Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

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Erik eHrabovszky

2013-09-01

Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.

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Chaudhari, Nirja; Dawalbhakta, Mitali; Nampoothiri, Laxmipriya

2018-04-11

GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS. PCOS was induced in rats by oral administration of letrozole (aromatase inhibitor). Following PCOS validation, animals were assessed for gonadotropin levels and their mRNA expression. Neurotrasnmitter status was evaluated by estimating their levels, their metabolism and their receptor expression in hypothalamus, pituitary, hippocampus and frontal cortex of PCOS rat model. We demonstrate that GnRH and LH inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are reduced while glutamate, a major stimulator of GnRH and LH release, is increased in the PCOS condition. Concomitant changes were observed for neurotransmitter metabolising enzymes and their receptors as well. Our results reveal that increased GnRH and LH pulsatility in PCOS condition likely result from the cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in hypothalamic-pituitary centre. This, we hypothesise, is responsible for the depression and anxiety-like mood disorders commonly seen in PCOS women.

[Revelation of a polymicrocystic ovary syndrome after one month's treatment by pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].

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Reyss, A C; Merlen, E; Demerle, C; Dewailly, D

2003-12-01

Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most frequent causes of endocrine infertility, but their association is an uncommon occurrence. We report the case of a 28-year old woman suffering from infertility and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant with the onset of amenorrhea. At the initial evaluation, the patient was considered as having HA due to food restriction. At ultrasonography, ovaries were small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively; number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile GnRH administration. Although the doses were increased from 5 to 15 microg/pulse every 90 min, no E2 response and no follicular development were observed. Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small cysts arranged peripherally around an increased central stroma in each ovary). The treatment has been then switched to hMG, using the low dose step-up regimen and starting with 75 U/day. In the absence of response after 2 weeks, the dose was increased to 112.5 U/day and a multifollicular reaction occurred, leading to cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS when she was hypogonadotrophic and that it developed very rapidly after restitution of a normal gonadotropin level under exogenous GnRH. This occurred despite a low insulin level, showing that hyperinsulinism is not a prerequisite for the development of PCOS in every case.

Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.

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Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

2014-07-01

In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5α-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. © 2014 Society for Endocrinology.

Melatonin Inhibits GnRH-1, GnRH-3 and GnRH Receptor Expression in the Brain of the European Sea Bass, Dicentrarchus labrax

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José Antonio Muñoz-Cueto

2013-04-01

Full Text Available Several evidences supported the existence of melatonin effects on reproductive system in fish. In order to investigate whether melatonin is involved in the modulation of GnRH systems in the European sea bass, we have injected melatonin (0.5 µg/g body mass in male specimens. The brain mRNA transcript levels of the three GnRH forms and the five GnRH receptors present in this species were determined by real time quantitative PCR. Our findings revealed day–night variations in the brain expression of GnRH-1, GnRH-3 and several GnRH receptors (dlGnRHR-II-1c, -2a, which exhibited higher transcript levels at mid-light compared to mid-dark phase of the photocycle. Moreover, an inhibitory effect of melatonin on the nocturnal expression of GnRH-1, GnRH-3, and GnRH receptors subtypes 1c, 2a and 2b was also demonstrated. Interestingly, the inhibitory effect of melatonin affected the expression of hypophysiotrophic GnRH forms and GnRH receptors that exhibit day–night fluctuations, suggesting that exogenous melatonin reinforce physiological mechanisms already established. These interactions between melatoninergic and GnRH systems could be mediating photoperiod effects on reproductive and other rhythmic physiological events in the European sea bass.

Hedgehog-PKA signaling and gnrh3 regulate the development of zebrafish gnrh3 neurons.

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Ming-Wei Kuo

Full Text Available GnRH neurons secrete GnRH that controls the development of the reproduction system. Despite many studies, the signals controlling the development of GnRH neurons from its progenitors have not been fully established. To understand the development of GnRH neurons, we examined the development of gnrh3-expressing cells using a transgenic zebrafish line that expresses green fluorescent protein (GFP and LacZ driven by the gnrh3 promoter. GFP and LacZ expression recapitulated that of gnrh3 in the olfactory region, olfactory bulb and telencephalon. Depletion of gnrh3 by morpholinos led to a reduction of GFP- and gnrh3-expressing cells, while over-expression of gnrh3 mRNA increased the number of these cells. This result indicates a positive feed-forward regulation of gnrh3 cells by gnrh3. The gnrh3 cells were absent in embryos that lack Hedgehog signaling, but their numbers were increased in embryos overexpressing shhb. We manipulated the amounts of kinase that antagonizes the Hedgehog signaling pathway, protein kinase A (PKA, by treating embryos with PKA activator forskolin or by injecting mRNAs encoding its constitutively active catalytic subunit (PKA* and dominant negative regulatory subunit (PKI into zebrafish embryos. PKA* misexpression or forskolin treatment decreased GFP cell numbers, while PKI misexpression led to ectopic production of GFP cells. Our data indicate that the Hedgehog-PKA pathway participates in the development of gnrh3-expressing neurons during embryogenesis.

A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH

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Reed Michael C

2004-09-01

Full Text Available Abstract In a previous study, a model was developed to investigate the release of luteinizing hormone (LH from pituitary cells in response to a short pulse of gonadotropin-releasing hormone (GnRH. The model included: binding of GnRH to its receptor (R, dimerization and internalization of the hormone receptor complex, interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3, release of calcium from the endoplasmic reticulum (ER, entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and release of LH. The extended model, presented in this paper, also includes the following physiologically important phenomena: desensitization of calcium channels; internalization of the dimerized receptors and recycling of some of the internalized receptors; an increase in Gq concentration near the plasma membrane in response to receptor dimerization; and basal rates of synthesis and degradation of the receptors. With suitable choices of the parameters, good agreement with a variety of experimental data of the LH release pattern in response to pulses of various durations, repetition rates, and concentrations of GnRH were obtained. The mathematical model allows us to assess the effects of internalization and desensitization on the shapes and time courses of LH response curves.

Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

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Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Pitteloud, Nelly; Seminara, Stephanie B.; Plummer, Lacey; Pignatelli, Duarte; Crowley, William F.; Welt, Corrine K.

2013-01-01

Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. PMID:23341491

Comparison of long GnRH agonist versus GnRH antagonist protocol in poor responders

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Sadık Şahin

2014-12-01

Full Text Available Objective: To compare long GnRH agonist with GnRH antagonist protocol in poor responders. Materials and Methods: Medical charts of 531 poor responder women undergoing in-vitro fertilization (IVF cycle at Zeynep Kamil Maternity and Children’s Hospital, IVF Center were retrospectively analysed. Those who received at least 300 IU/daily gonadotropin and had ≤3 oocytes retrieved were enrolled in the study. Poor responders were categorized into two groups as those who received long GnRH agonist or GnRH antagonist regimen. Results: Treatment duration and total gonadotropin dosage were significantly higher in women undergoing the long GnRH agonist regimen compared with the GnRH antagonist regimen (p<0.001 for both. Although the number of total and mature oocytes retrieved was similar between the groups, good quality embryos were found to be higher in the GnRH antagonist regimen. The day of embryo transfer and number of transferred embryos were similar in the groups. No statistically significant differences were detected in pregnancy (10.5% vs 14.1%, clinical pregnancy (7.7% vs 10.6% and early pregnancy loss rates (27.2% vs 35% between the groups. Conclusion: GnRH antagonist regimen may be preferable to long GnRH regimen as it could decrease the cost and treatment duration in poor responders.

Evaluation of the pituitary-gonadal response to GnRH, and adrenal status, in the leopard (Panthera pardus japonensis) and tiger (Panthera tigris).

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Brown, J L; Goodrowe, K L; Simmons, L G; Armstrong, D L; Wildt, D E

1988-01-01

Frequent blood samples were collected to study hormonal responses to GnRH in male and female leopards and tigers. Animals were anaesthetized with ketamine-HCl and blood samples were collected every 5 min for 15 min before and 160 min after i.v. administration of GnRH (1 micrograms/kg body weight) or saline. No differences in serum cortisol concentrations were observed between sexes within species, but mean cortisol was 2-fold greater in leopards than tigers. GnRH induced a rapid rise in LH in all animals (18.3 +/- 0.9 min to peak). Net LH peak height above pretreatment levels was 3-fold greater in males than conspecific females and was also greater in tigers than leopards. Serum FSH increased after GnRH, although the magnitude of response was less than that observed for LH. Basal LH and FSH and GnRH-stimulated FSH concentrations were not influenced by sex or species. Serum testosterone increased within 30-40 min after GnRH in 3/3 leopard and 1/3 tiger males. Basal testosterone was 3-fold greater in tiger than leopard males. LH pulses (1-2 pulses/3 h) were detected in 60% of saline-treated animals, suggesting pulsatile gonadotrophin secretion; however, in males concomitant testosterone pulses were not observed. These results indicate that there are marked sex and species differences in basal and GnRH-stimulated hormonal responses between felids of the genus Panthera which may be related to differences in adrenal activity.

Modeling the Male Reproductive Endocrine Axis: Potential Role for a Delay Mechanism in the Inhibitory Action of Gonadal Steroids on GnRH Pulse Frequency.

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Ferasyi, Teuku R; Barrett, P Hugh R; Blache, Dominique; Martin, Graeme B

2016-05-01

We developed a compartmental model so we could test mechanistic concepts in the control of the male reproductive endocrine axis. Using SAAM II computer software and a bank of experimental data from male sheep, we began by modeling GnRH-LH feed-forward and LH-T feedback. A key assumption was that the primary control signal comes from a hypothetical neural network (the PULSAR) that emits a digital (pulsatile) signal of variable frequency that drives GnRH secretion in square wave-like pulses. This model produced endocrine profiles that matched experimental observations for the testis-intact animal and for changes in GnRH pulse frequency after castration and T replacement. In the second stage of the model development, we introduced a delay in the negative feedback caused by the aromatization of T to estradiol at the brain level, a concept supported by empirical observations. The simulations showed how changes in the process of aromatization could affect the response of the pulsatile signal to inhibition by steroid feedback. The sensitivity of the PULSAR to estradiol was a critical factor, but the most striking observation was the effect of time delays. With longer delays, there was a reduction in the rate of aromatization and therefore a decrease in local estradiol concentrations, and the outcome was multiple-pulse events in the secretion of GnRH/LH, reflecting experimental observations. In conclusion, our model successfully emulates the GnRH-LH-T-GnRH loop, accommodates a pivotal role for central aromatization in negative feedback, and suggests that time delays in negative feedback are an important aspect of the control of GnRH pulse frequency.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET

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Depalo Raffaella

2012-04-01

Full Text Available Abstract Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Ontogenic and sexual differences in pituitary GnRH receptors and intracellular Ca2+ mobilization induced by GnRH.

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Lacau-Mengido, I M; González Iglesias, A; Lux-Lantos, V; Libertun, C; Becú-Villalobos, D

1998-04-01

The present experiments were designed in order to elucidate the participation of the developing hypophysis in determining the changing sensitivity of gonadotrophins to gonadotropin-releasing hormone (GnRH) during ontogeny in the rat. To that end, we chose two well defined developmental ages that differ markedly in sexual and ontogenic characteristics of hypophyseal sensitivity to GnRH, 15 and 30 d. In order to study sex differences and the role of early sexual organization of the hypothalamus, experiments were carried out in males, females, and neonatally androgenized females (TP females). We evaluated (1) the characteristics of pituitary GnRH receptors, and (2) associated changes in GnRH-induced mobilization of intracellular Ca2+ (a second messenger involved in gonadotropins exocytosis). We measured binding characteristics of the GnRH analog D-Ser(TBu)6-des-Gly10-GnRH ethylamide in pituitary homogenates. We found that Kds did not vary among the different sex groups. Total number and concentration of receptors decreased in the female rat from 15-30 d of age, whereas in the male and TP female, receptors/pituitary increased, and the concentration/mg tissue did not change. Also, at 30 days of age, males presented higher content and concentration of receptors than females, and higher content than TP females. In order to evaluate if developmental and sexual differences in pituitary sensitivity to GnRH might be expressed through variations in the intracellular Ca2+ signal, we studied the mobilization of intracellular Ca2+ induced by GnRH (1 x 10(-8) to 1 x 10(-11) M) in a suspension of dispersed pituitary cells in the six groups. In cells from 15-d-old females, Ca2+ response was greater than in 30-d-old females at the doses of 10(-8) to 10(-10) M, indicating that in the infantile female rat activation of highly concentrated GnRH receptors is reflected in an increase in signal transduction mediated by Ca2+. In males and in female rats androgenized at birth, there was also

Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

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Stefan Lim

Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology

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Stenbæk, D. S.; Toftager, M.; Hjordt, L. V.

2015-01-01

STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? SUMMARY ANSWER: ART treatment did not induce elevated levels...... of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY: ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological...... characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment. STUDY DESIGN, SIZE, DURATION: A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist...

A neurokinin 3 receptor-selective agonist accelerates pulsatile luteinizing hormone secretion in lactating cattle.

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Nakamura, Sho; Wakabayashi, Yoshihiro; Yamamura, Takashi; Ohkura, Satoshi; Matsuyama, Shuichi

2017-07-01

Pulsatile gonadotropin-releasing hormone (GnRH) secretion, which is indispensable for follicular development, is suppressed in lactating dairy and beef cattle. Neurokinin B (NKB) neurons in the arcuate nucleus of the hypothalamus are considered to play an essential role in generating the pulsatile mode of GnRH/luteinizing hormone (LH) secretion. The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/gonadotropin secretion in postpartum lactating cattle. We examined the effects of the administration of an NK3R-selective agonist, senktide, on gonadotropin secretion in lactating cattle. The lactating cattle, at approximately 7 days postpartum, were intravenously infused with senktide (30 or 300 nmol/min) or vehicle for 24 h. The administration of 30 or 300 nmol/min senktide significantly increased LH pulse frequency compared to in the control group during 0-4 or 20-24 h after infusion, respectively. Moreover, LH and follicle-stimulating hormone levels were gradually increased by 300 nmol/min administration of senktide during the 0-4-h sampling period. Ultrasonography of the ovaries was performed to identify the first postpartum ovulation in senktide-administered lactating cattle. The interval from calving to first postpartum ovulation was significantly shorter in the 300 nmol/min senktide-administered group than in the control group. Taken together, these findings suggest that senktide infusion elicits an increase in LH pulse frequency that may stimulate follicular development and, in turn, induce the first postpartum ovulation in lactating cattle. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A conserved non-reproductive GnRH system in chordates.

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Takehiro G Kusakabe

Full Text Available Gonadotropin-releasing hormone (GnRH is a neuroendocrine peptide that plays a central role in the vertebrate hypothalamo-pituitary axis. The roles of GnRH in the control of vertebrate reproductive functions have been established, while its non-reproductive function has been suggested but less well understood. Here we show that the tunicate Ciona intestinalis has in its non-reproductive larval stage a prominent GnRH system spanning the entire length of the nervous system. Tunicate GnRH receptors are phylogenetically closest to vertebrate GnRH receptors, yet functional analysis of the receptors revealed that these simple chordates have evolved a unique GnRH system with multiple ligands and receptor heterodimerization enabling complex regulation. One of the gnrh genes is conspicuously expressed in the motor ganglion and nerve cord, which are homologous structures to the hindbrain and spinal cord of vertebrates. Correspondingly, GnRH receptor genes were found to be expressed in the tail muscle and notochord of embryos, both of which are phylotypic axial structures along the nerve cord. Our findings suggest a novel non-reproductive role of GnRH in tunicates. Furthermore, we present evidence that GnRH-producing cells are present in the hindbrain and spinal cord of the medaka, Oryzias latipes, thereby suggesting the deep evolutionary origin of a non-reproductive GnRH system in chordates.

GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

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Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

2013-01-01

The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

Surface obstacles in pulsatile flow

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Carr, Ian A.; Plesniak, Michael W.

2017-11-01

Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e., constant velocity, unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigate the wake of two canonical obstacles: a cube and a circular cylinder with an aspect ratio of unity. Our previous studies of a surface-mounted hemisphere in pulsatile flow are used as a baseline for these two new, more complex geometries. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

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Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The pmicrodose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

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Parisa Khani

2013-01-01

Full Text Available Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasinghormone (GnRH agonist flare combined with the fixed multidose GnRH antagonistprotocol in poor responders undergoing ovarian stimulation.Materials and Methods: In this randomized clinical trial, 120 women who were candidates forassisted reproductive techniques (ART and had histories of one or more failed in vitro fertilization(IVF cycles with three or fewer retrieved oocytes were prospectively randomized into two groups.Group I (60 patients received the microdose flare-up regimen and group II (60 patients receivedthe ultrashort GnRH agonist combined with fixed GnRH antagonist.Results: There were no significant differences between the groups in the number of used gonadotropinampoules (p=0.591, duration of stimulation (p=0.610, number of retrieved oocytes (p=0.802,fertilization rate (p=0.456, and the number of transferred embryos (p=0.954. The clinical pregnancyrates were statistically similar in group I (10% compared with group II (13.3%, p=0.389.Conclusion: According to our results, there is no significant difference between these protocolsfor improving the ART outcome in poor responders. Additional prospective, randomizedstudies with more patients is necessary to determine the best protocol (Registration Number:IRCT201105096420N1.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

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Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

Pulmonary O2 transfer during pulsatile and non-pulsatile perfusion.

Science.gov (United States)

Hauge, A; Nicolaysen, G

1980-07-01

The importance of the perfusion pattern for the oxygen transfer has been examined in isolated rabbit lungs perfused with plasma at constant volume inflow. The lungs were ventilated with constant tidal volume and constant end-expiratory pressure. Following a standardized rise in FIO2 the rate of rise in pulmonary venous PO2 (delta PO2/delta t) was measured during alternately pulsatile and non-pulsatile perfusion in normal lungs and in lungs made edematous by elevation of left atrial pressure. In normal lungs there was no difference in delta PO2/delta t when the two modes of perfusion were compared. In edematous lungs delta PO/delta t was statistically higher during pulsatile perfusion, indicating a beneficial effect of flow- and pressure pulsations, e.g. a better distribution of V/Q ratios throughout the lungs. In a separate series of expts. the advancement of a high O2 front through the airways was measured, and the two perfusion patterns compared. Since no difference was found, we suggest that the phenomenon of "cardiogenic gas mixing" in the airways in vivo is a result of a direct action of the heart on the lungs rather than arterial pulsations.

Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol

DEFF Research Database (Denmark)

Toftager, M.; Bogstad, J; Bryndorf, T

2016-01-01

interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta...... IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS...... between the two arms. None of the women had undergone previous ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total...

Cloning and functional analysis of promoters of three GnRH genes in a cichlid

International Nuclear Information System (INIS)

Kitahashi, Takashi; Sato, Hideki; Sakuma, Yasuo; Parhar, Ishwar S.

2005-01-01

Mechanisms regulating gonadotropin-releasing hormone (GnRH) types, a key molecule for reproductive physiology, remain unclear. In the present study, we cloned the promoters of GnRH1, GnRH2, and GnRH3 genes in the tilapia, Oreochromis niloticus; and found putative binding sites for glucocorticoid receptors, Sp1, C/EBP, GATA, and Oct-1, but not for androgen receptors in all three GnRH promoters using computer analysis. The presence of binding sites for progesterone receptors in GnRH1, estrogen receptors in GnRH1 and GnRH2, and thyroid hormone receptors in GnRH1 and GnRH3 suggests direct action of steroid hormones on GnRH types. Our observation of SOX and LINE-like sequences exclusively in GnRH1, COUP in GnRH2, and retinoid X receptors in GnRH3 suggests their role in sexual differentiation, midbrain segmentation, and visual cue integration, respectively. Thus, the characteristic binding sites for nuclear receptors and transcription factors support the notion that each GnRH type is regulated differently and has distinct physiological roles

Effects of GnRH immunization in sexually mature pony stallions

NARCIS (Netherlands)

Turkstra, J.A.; Meer, F.J.U.M.; Knaap, J.; Rottier, P.J.M.; Teerds, K.J.; Colenbrander, B.; Meloen, R.H.

2005-01-01

Immunization against gonadotrophin releasing hormone (GnRH) was studied as an alternative for the commonly used surgical castration in stallions. Two GnRH vaccines comprising non-mineral oil adjuvants were evaluated for their potential to induce high antibody titers directed against GnRH and

Fanconi Anemia a Is a Nucleocytoplasmic Shuttling Molecule Required for Gonadotropin-Releasing Hormone (GnRH) Transduction of the GnRH Receptor

OpenAIRE

Larder, Rachel; Karali, Dimitra; Nelson, Nancy; Brown, Pamela

2006-01-01

GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on pituitary gonadotropes and drives expression of gonadotropin hormones. There are two gonadotropin hormones, comprised of a common α- and hormone-specific β-subunit, which are required for gonadal function. Recently we identified that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed within the LβT2 gonadotrope cell line in response to stimulation with GnRH. FANCA is mutated in more than 60%...

Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

Directory of Open Access Journals (Sweden)

Abbas Aflatoonian

2017-08-01

Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

The role of GABA in the regulation of GnRH neurons

Directory of Open Access Journals (Sweden)

Miho eWatanabe

2014-11-01

Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

Imaging in pulsatile tinnitus

International Nuclear Information System (INIS)

Madani, G.; Connor, S.E.J.

2009-01-01

Tinnitus may be continuous or pulsatile. Vascular lesions are the most frequent radiologically demonstrable cause of pulsatile tinnitus. These include congenital vascular anomalies (which may be arterial or venous), vascular tumours, and a variety of acquired vasculopathies. The choice of imaging depends on the clinical findings. If a mass is present at otoscopy, thin-section computed tomography (CT) is indicated. In the otoscopically normal patient, there is a range of possible imaging approaches. However, combined CT angiography and venography is particularly useful

Imaging in pulsatile tinnitus

Energy Technology Data Exchange (ETDEWEB)

Madani, G. [Radiology Department, St Mary' s Hospital, London (United Kingdom)], E-mail: gittamadani@yahoo.com; Connor, S E.J. [Neuroradiology Department, King' s College Hospital, London (United Kingdom)

2009-03-15

Tinnitus may be continuous or pulsatile. Vascular lesions are the most frequent radiologically demonstrable cause of pulsatile tinnitus. These include congenital vascular anomalies (which may be arterial or venous), vascular tumours, and a variety of acquired vasculopathies. The choice of imaging depends on the clinical findings. If a mass is present at otoscopy, thin-section computed tomography (CT) is indicated. In the otoscopically normal patient, there is a range of possible imaging approaches. However, combined CT angiography and venography is particularly useful.

Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.

Science.gov (United States)

Devjak, Rok; Fon Tacer, Klementina; Juvan, Peter; Virant Klun, Irma; Rozman, Damjana; Vrtačnik Bokal, Eda

2012-01-01

In in vitro fertilization (IVF) cycles controlled ovarian hyperstimulation (COH) is established by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists, to prevent premature luteinizing hormone (LH) surge. The aim of our study was to improve the understanding of gene expression profile of cumulus cells (CC) in terms of ovarian stimulation protocol and oocyte maturity. We applied Affymetrix gene expression profiling in CC of oocytes at different maturation stages using either GnRH agonists or GnRH antagonists. Two analyses were performed: the first involved CC of immature metaphase I (MI) and mature metaphase II (MII) oocytes where 359 genes were differentially expressed, and the second involved the two GnRH analogues where no differentially expressed genes were observed at the entire transcriptome level. A further analysis of 359 differentially genes was performed, focusing on anti-Müllerian hormone receptor 2 (AMHR2), follicle stimulating hormone receptor (FSHR), vascular endothelial growth factor C (VEGFC) and serine protease inhibitor E2 (SERPINE2). Among other differentially expressed genes we observed a marked number of new genes connected to cell adhesion and neurotransmitters such as dopamine, glycine and γ-Aminobutyric acid (GABA). No differential expression in CC between the two GnRH analogues supports the findings of clinical studies where no significant difference in live birth rates between both GnRH analogues has been proven.

Origins of gonadotropin-releasing hormone (GnRH) in vertebrates: identification of a novel GnRH in a basal vertebrate, the sea lamprey.

Science.gov (United States)

Kavanaugh, Scott I; Nozaki, Masumi; Sower, Stacia A

2008-08-01

We cloned a cDNA encoding a novel (GnRH), named lamprey GnRH-II, from the sea lamprey, a basal vertebrate. The deduced amino acid sequence of the newly identified lamprey GnRH-II is QHWSHGWFPG. The architecture of the precursor is similar to that reported for other GnRH precursors consisting of a signal peptide, decapeptide, a downstream processing site, and a GnRH-associated peptide; however, the gene for lamprey GnRH-II does not have introns in comparison with the gene organization for all other vertebrate GnRHs. Lamprey GnRH-II precursor transcript was widely expressed in a variety of tissues. In situ hybridization of the brain showed expression and localization of the transcript in the hypothalamus, medulla, and olfactory regions, whereas immunohistochemistry using a specific antiserum showed only GnRH-II cell bodies and processes in the preoptic nucleus/hypothalamus areas. Lamprey GnRH-II was shown to stimulate the hypothalamic-pituitary axis using in vivo and in vitro studies. Lamprey GnRH-II was also shown to activate the inositol phosphate signaling system in COS-7 cells transiently transfected with the lamprey GnRH receptor. These studies provide evidence for a novel lamprey GnRH that has a role as a third hypothalamic GnRH. In summary, the newly discovered lamprey GnRH-II offers a new paradigm of the origin of the vertebrate GnRH family. We hypothesize that due to a genome/gene duplication event, an ancestral gene gave rise to two lineages of GnRHs: the gnathostome GnRH and lamprey GnRH-II.

Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

Directory of Open Access Journals (Sweden)

Christian Cortés-Campos

2015-09-01

Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

Biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in hypothalamic-pituitary unit of anoestrous and cyclic ewes.

Science.gov (United States)

Ciechanowska, M O; Łapot, M; Mateusiak, K; Paruszewska, E; Malewski, T; Przekop, F

2017-02-01

This study was performed to explain how the molecular processes governing the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit are reflected by luteinizing hormone (LH) secretion in sheep during anoestrous period and during luteal and follicular phases of the oestrous cycle. Using an enzyme-linked immunosorbent assay (ELISA), we analyzed the levels of GnRH and GnRHR in preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk-median eminence (SME), and GnRHR in the anterior pituitary gland (AP). Radioimmunoassay has also been used to define changes in plasma LH concentrations. The study provides evidence that the levels of GnRH in the whole hypothalamus of anoestrous ewes were lower than that in sheep during the follicular phase of the oestrous cycle (POA: p pituitary unit, as well as LH level, in the blood in anoestrous ewes were significantly lower than those detected in animals of both cyclic groups. Our data suggest that decrease in LH secretion during the long photoperiod in sheep may be due to low translational activity of genes encoding both GnRH and GnRHR.

Does the location of a vascular loop in the cerebellopontine angle explain pulsatile and non-pulsatile tinnitus?

International Nuclear Information System (INIS)

Nowe, V.; Wang, X.L.; Gielen, J.; Goethem, J.Van; Oezsarlak, Oe.; De Schepper, A.M.; Parizel, P.M.; Ridder, D. De; Heyning, P.H.Van de

2004-01-01

The purpose was to investigate patients with unexplained pulsatile and non-pulsatile tinnitus by means of MR imaging of the cerebellopontine angle (CPA) and to correlate the clinical subtype of tinnitus with the location of a blood vessel (in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve). Clinical presentation of tinnitus and perceptive hearing loss were correlated. In 47 patients with unexplained tinnitus, an MR examination of the CPA was performed. Virtual endoscopy reconstructions were obtained using a 3D axial thin-section high-resolution heavily T2-weighted gradient echo constructive interference in steady state (CISS) data-set. High-resolution T2-weighted CISS images showed a significantly higher number of vascular loops in the internal auditory canal in patients with arterial pulsatile tinnitus compared to patients with non-pulsatile tinnitus (P<0.00001). Virtual endoscopy images were used to investigate vascular contacts at the cisternal part of the VIIIth cranial nerve in patients with low pitch and high pitch non-pulsatile tinnitus. A significantly different distribution of the vascular contacts (P=0.0320) was found. Furthermore, a correlation between the clinical presentation of non-pulsatile tinnitus (high pitch and low pitch) and the perceptive hearing loss was found (P=0.0235). High-resolution heavily T2-weighted CISS images and virtual endoscopy of the CPA can be used to evaluate whether a vascular contact is present in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve and whether the location of the vascular contact correlates with the clinical subtype of tinnitus. Our findings suggest that there is a tonotopical structure of the cisternal part of the VIIIth cranial nerve. A correlation between the clinical presentation of tinnitus and hearing loss was found. (orig.)

Does the location of a vascular loop in the cerebellopontine angle explain pulsatile and non-pulsatile tinnitus?

Energy Technology Data Exchange (ETDEWEB)

Nowe, V; Wang, X L; Gielen, J; Goethem, J Van; Oezsarlak, Oe; De Schepper, A M; Parizel, P M [University of Antwerp, Department of Radiology, Edegem (Belgium); Ridder, D De [University of Antwerp, Department of Neurosurgery, Edegem (Belgium); Heyning, P.H.Van de [University of Antwerp, Department of Otorhinolaryngology, Edegem (Belgium)

2004-12-01

The purpose was to investigate patients with unexplained pulsatile and non-pulsatile tinnitus by means of MR imaging of the cerebellopontine angle (CPA) and to correlate the clinical subtype of tinnitus with the location of a blood vessel (in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve). Clinical presentation of tinnitus and perceptive hearing loss were correlated. In 47 patients with unexplained tinnitus, an MR examination of the CPA was performed. Virtual endoscopy reconstructions were obtained using a 3D axial thin-section high-resolution heavily T2-weighted gradient echo constructive interference in steady state (CISS) data-set. High-resolution T2-weighted CISS images showed a significantly higher number of vascular loops in the internal auditory canal in patients with arterial pulsatile tinnitus compared to patients with non-pulsatile tinnitus (P<0.00001). Virtual endoscopy images were used to investigate vascular contacts at the cisternal part of the VIIIth cranial nerve in patients with low pitch and high pitch non-pulsatile tinnitus. A significantly different distribution of the vascular contacts (P=0.0320) was found. Furthermore, a correlation between the clinical presentation of non-pulsatile tinnitus (high pitch and low pitch) and the perceptive hearing loss was found (P=0.0235). High-resolution heavily T2-weighted CISS images and virtual endoscopy of the CPA can be used to evaluate whether a vascular contact is present in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve and whether the location of the vascular contact correlates with the clinical subtype of tinnitus. Our findings suggest that there is a tonotopical structure of the cisternal part of the VIIIth cranial nerve. A correlation between the clinical presentation of tinnitus and hearing loss was found. (orig.)

Fanconi anemia A is a nucleocytoplasmic shuttling molecule required for gonadotropin-releasing hormone (GnRH) transduction of the GnRH receptor.

Science.gov (United States)

Larder, Rachel; Karali, Dimitra; Nelson, Nancy; Brown, Pamela

2006-12-01

GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on pituitary gonadotropes and drives expression of gonadotropin hormones. There are two gonadotropin hormones, comprised of a common alpha- and hormone-specific beta-subunit, which are required for gonadal function. Recently we identified that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially expressed within the LbetaT2 gonadotrope cell line in response to stimulation with GnRH. FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility. Here we show that induction of FANCA protein is mediated by the GnRHR and that the protein constitutively adopts a nucleocytoplasmic intracellular distribution pattern. Using inhibitors to block nuclear import and export and a GnRHR antagonist, we demonstrated that GnRH induces nuclear accumulation of FANCA and green fluorescent protein (GFP)-FANCA before exporting back to the cytoplasm using the nuclear export receptor CRM1. Using FANCA point mutations that locate GFP-FANCA to the cytoplasm (H1110P) or functionally uncouple GFP-FANCA (Q1128E) from the wild-type nucleocytoplasmic distribution pattern, we demonstrated that wild-type FANCA was required for GnRH-induced activation of gonadotrope cell markers. Cotransfection of H1110P and Q1128E blocked GnRH activation of the alphaGsu and GnRHR but not the beta-subunit gene promoters. We conclude that nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the alphaGSU and GnRHR gene promoters and propose that FANCA functions as a GnRH-induced signal transducer.

GnRH injection before artificial insemination (AI) alters follicle ...

African Journals Online (AJOL)

STORAGESEVER

2009-08-04

Aug 4, 2009 ... releasing hormone (GnRH) injection on day 6 of the estrous cycle. The estrous cycles ... follicle at the time of GnRH injection (Silcox et al., 1993;. Twagiramungu .... Waves and their Effect on pregnancy rate in the Cow. Reprod.

Gonadotropin-releasing hormone for infertility in women with primary hypothalamic amenorrhea. Toward a more-interventional approach.

Science.gov (United States)

Kesrouani, A; Abdallah, M A; Attieh, E; Abboud, J; Atallah, D; Makhoul, C

2001-01-01

To assess the effectiveness of a protocol of pulsatile gonadotropin releasing-hormone (GnRH) in treating infertility in women with primary hypothalamic amenorrhea. Retrospective analysis of 44 cycles treated at an infertility center. Twenty-four patients with primary hypothalamic amenorrhea were treated intravenously with pulsatile GnRH using 5 micrograms per bolus every 90 minutes. Ultrasound monitoring and cervical assessment by Insler's scoring system allowed timed injection of human chorionic gonadotropin (hCG) and intrauterine insemination if needed. Luteal support was provided with hCG. The ovulation rate was 95% with the 5-microgram dose. A single follicle was produced in 91% of cycles. The overall pregnancy rate per ovulatory cycle was 45%, and the pregnancy rate per patient was 83%. In patients treated previously with exogenous gonadotropins, poor results were observed. Only one case of mild overstimulation was reported. Pulsatile GnRH is an effective and safe method of treating infertility in women with primary hypothalamic amenorrhea, thus simulating normal ovulation; however, more-interventional management, including the qualitative estrogenic response, may lead to optimal results and increase the pregnancy rate.

Genetics of Isolated Hypogonadotropic Hypogonadism: Role of GnRH Receptor and Other Genes

Directory of Open Access Journals (Sweden)

Karges Beate

2012-01-01

Full Text Available Hypothalamic gonadotropin releasing hormone (GnRH is a key player in normal puberty and sexual development and function. Genetic causes of isolated hypogonadotropic hypogonadism (IHH have been identified during the recent years affecting the synthesis, secretion, or action of GnRH. Developmental defects of GnRH neurons and the olfactory bulb are associated with hyposmia, rarely associated with the clinical phenotypes of synkinesia, cleft palate, ear anomalies, or choanal atresia, and may be due to mutations of KAL1, FGFR1/FGF8, PROKR2/PROK2, or CHD7. Impaired GnRH secretion in normosmic patients with IHH may be caused by deficient hypothalamic GPR54/KISS1, TACR3/TAC3, and leptinR/leptin signalling or mutations within the GNRH1 gene itself. Normosmic IHH is predominantly caused by inactivating mutations in the pituitary GnRH receptor inducing GnRH resistance, while mutations of the β-subunits of LH or FSH are very rare. Inheritance of GnRH deficiency may be oligogenic, explaining variable phenotypes. Future research should identify additional genes involved in the complex network of normal and disturbed puberty and reproduction.

Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

Science.gov (United States)

Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

1985-09-01

We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the

GnRH mRNA levels in male three-spined sticklebacks, Gasterosteus aculeatus, under different reproductive conditions.

Science.gov (United States)

Shao, Yi Ta; Tseng, Yung Che; Chang, Chia-Hao; Yan, Hong Young; Hwang, Pung Pung; Borg, Bertil

2015-02-01

In vertebrates, reproduction is regulated by the brain-pituitary-gonad (BPG) axis, where the gonadotropin-releasing hormone (GnRH) is one of the key components. However, very little is known about the possible role of GnRH in the environmental and feedback control of fish reproduction. To investigate this, full-length gnrh2 (chicken GnRH II) and gnrh3 (salmon GnRH) sequences of male three-spined sticklebacks (Gasterosteus aculeatus), which are clustered with the taxa of the same GnRH type as other Euteleostei, were cloned and annotated. gnrh1 is absent in this species. The mRNA levels of gnrh2 and gnrh3 in the sticklebacks' brain were measured under breeding and post-breeding conditions as well as in castrated and sham-operated breeding fish and castrated/sham-operated fish kept under long-day (LD 16:8) and short-day (LD 8:16) conditions. Fully breeding males had considerably higher mRNA levels of gnrh2 and gnrh3 in the thalamus (Th) and in the telencephalon and preoptic area (T+POA), respectively, than post-breeding males. Sham-operated breeding males have higher gnrh3 mRNA levels than the corresponding castrated males. Moreover, higher gnrh2 mRNA levels in the Th and higher gnrh3 mRNA levels in the T+POA and hypothalamus (HypTh) were also found in long-day sham-operated males than in sham-operated fish kept under an inhibitory short day photoperiod. Nevertheless, gnrh2 and gnrh3 mRNA levels were not up-regulated in castrated males kept under long-day photoperiod, which suggests that positive feedbacks on the brain-pituitary-gonad axis are necessary for this response. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of the GnRH-(1-5) Receptor and Signaling Pathway

Science.gov (United States)

2013-03-22

expression in immortalized GnRH neurons and to facilitate lordosis behavior in female rats. Interestingly, EP24.15 colocalizes with vii...expression in immortalized GnRH neurons (73) and facilitates lordosis behavior in female rats (72). Interestingly, EP24.15 is expressed along the...biologically active by facilitating lordosis behavior in ovariectomized estrogen-primed rats (72); and can increase the mRNA expression of GnRH in immortalized

Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio Reveals No Effects on Reproductive Performance.

Directory of Open Access Journals (Sweden)

Olivia Smith Spicer

Full Text Available Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form function in zebrafish (Danio rerio to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored.

AN OVERVIEW ON PULSATILE FLOW DYNAMICS

OpenAIRE

Çarpinlioğlu, Melda Özdinç

2015-01-01

Pulsatile flow dynamics in reference to the relevant experimental research on the manner between the time periods of 1997- 2015 is presented in this paper. The flow field under discussion is generated through a rigid circular cross-sectional pipe as an axial slightly- compressible and sinusoidal one in a controlled range of the oscillation parameters. Laminar and turbulent flow regimes are considered with a particular emphasis devoted to the transitional characteristics of laminar pulsatile f...

In vitro regulation of LH biosynthesis and release by GnRH and estradiol

International Nuclear Information System (INIS)

Ramey, J.W.

1986-01-01

Anterior pituitaries were taken from female rats at random stages of the estrous cycle, enzymatically dispersed, and cultured for 48h in steroid-free α-modified Eagles medium followed by 24h in fresh medium +/- estradiol (E 2 ). The pituitary cells were then incubated in fresh medium containing radiolabeled precursors +/- gonadotropin releasing hormone (GnRH). Radioactive precursor incorporation into LH was determined by immuno-precipitation. The dose-dependent effects of E 2 (10 -11 to 10 -8 M) on 3 H-glucosamine ( 3 H-Gln) and 35 S-methionine ( 35 S-Met) incorporation into LH +/- 1 nM GnRH (4h) were investigated. GnRH (10 -9 M) and E 2 (all doses) significantly increased total 3 H-Gln LH. Moreover, E 2 at 10 -9 M and 10 -8 M significantly enhanced GnRH stimulated LH glycosylation. In contrast, addition of GnRH and/or E 2 did not significantly increase 35 S-Met incorporation into LH over a 4h period. The effects of various GnRH concentrations (10 -11 to 10 -9 M; 8h) +/- E 2 (0.05 nM) on 3 H-Gln LH and 35 S-Met LH production were also investigated. In the absence of E 2 , only 10 -9 M GnRH was effective in increasing total 3 H-Gln LH and 35 S-Met LH synthesis. However, in the presence of E 2 , all concentrations of GnRH stimulated LH synthesis with 3 H-Gln LH production responding in a dose related manner whereas 35 S-Met LH production was maximally stimulated at all doses of GnRH. In the final series of experiments, pituitary cells previously exposed to estradiol were incubated for 4 h in normal calcium or low calcium medium containing 3 H-Gln or 35 S-Met +/- GnRH. Removal of extracellular calcium completely inhibited GnRH stimulated 3 H-Gln LH and 35 S-Met LH production

Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome

DEFF Research Database (Denmark)

Iliodromiti, Stamatina; Lan, Vuong Thi Ngoc; Tuong, Ho Manh

2013-01-01

Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implanta......Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory...... implantation rates can be sustained. The objective of this study was to assess the live-birth rate and incidence of OHSS after GnRHa trigger and intensive luteal steroid support compared to traditional hCG trigger and conventional luteal support in OHSS high risk Asian patients....

[Neuroendocrine mechanisms of puberty onset].

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Teinturier, C

2002-10-01

An increase in pulsatile release of GnRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in GnRH release is still unclear. The GnRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state by central inhibition in the juvenile period. When this central inhibition is removed or diminished, an increase in GnRH release occurs with increase in synthesis and release of gonadotropins and gonadal steroids, followed by the appearance of secondary sexual characteristics. Recent studies suggest that disinhibition of GnRH neurons from GABA (gamma-aminobutyric acid) appears to be a critical factor in female rhesus monkey. After central inhibition is removed, increases in stimulatory input from glutamatergic neurons as well as new stimulatory input from norepinephrine and NPY neurons and inhibitory input from beta endorphin neurons appear to control pulsatile GnRH release as well as gonadal steroids. Nonetheless, the most important question still remains: what determines the timing to remove central inhibition? Because many genes are turned on or turned off to establish a complex series of events occurring during puberty, the timing of puberty must be regulated by a master gene or genes, as a part of developmental events.

Differential Effects of Continuous Exposure to the Investigational Metastin/Kisspeptin Analog TAK-683 on Pulsatile and Surge Mode Secretion of Luteinizing Hormone in Ovariectomized Goats

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TANAKA, Tomomi; OHKURA, Satoshi; WAKABAYASHI, Yoshihiro; KUROIWA, Takenobu; NAGAI, Kiyosuke; ENDO, Natsumi; TANAKA, Akira; MATSUI, Hisanori; KUSAKA, Masami; OKAMURA, Hiroaki

2013-01-01

Abstract The aim of the present study was to determine if the estradiol-induced luteinizing hormone (LH) surge is influenced by the constant exposure to TAK-683, an investigational metastin/kisspeptin analog, that had been established to depress the pulsatile gonadotropin-releasing hormone (GnRH) and LH secretion in goats. Ovariectomized goats subcutaneously received TAK-683 (TAK-683 group, n=6) or vehicle (control group, n=6) constantly via subcutaneous implantation of an osmotic pump. Five days after the start of the treatment, estradiol was infused intravenously in both groups to evaluate the effects on the LH surge. Blood samples were collected at 6-min intervals for 4 h prior to the initiation of either the TAK-683 treatment or the estradiol infusion, to determine the profiles of pulsatile LH secretion. They were also collected at 2-h intervals from –4 h to 32 h after the start of estradiol infusion for analysis of LH surges. The frequency and mean concentrations of LH pulses in the TAK-683 group were remarkably suppressed 5 days after the start of TAK-683 treatment compared with those of the control group (P<0.05). On the other hand, a clear LH surge was observed in all animals of both groups. There were no significant differences in the LH concentrations for surge peak and the peak time of the LH surge between the TAK-683 and control groups. These findings suggest that the effects of continuous exposure to kisspeptin or its analog on the mechanism(s) that regulates the pulsatile and surge mode secretion of GnRH/LH are different in goats. PMID:24047956

Regulation versus modulation in GnRH receptor function

International Nuclear Information System (INIS)

Zolman, J.C.; Theodoropoulos, T.J.

1985-01-01

Serum luteinizing hormone (LH) concentration after exposure to gonadotropin-releasing hormone (GnRH) indicates that an instantaneous increase occurs in the rate of release of LH directly from the anterior pituitary, as measured dynamically during superfusion in vitro. On the other hand, estradiol-17 beta (E2) alone shows no such instantaneous effect on LH release rate (at least for the first four hours), in either physiologic or pharmacologic concentrations. At the same time, brief (ten to 30 minute) exposure of isolated anterior pituitary plasma membranes to physiologic concentrations of E2 significantly alters the binding of a fully biologically active 125 I-GnRH to its plasma membrane receptor protein. In order to characterize the effect of E2 on GnRH binding further, dispersed bovine anterior pituitary cells were preincubated for six hours in the presence or absence of physiologic concentrations of E2 (10(-10)M). Following preincubation in the presence of E2, the cell suspension was incubated for 30 minutes with physiologic concentrations (5 x 10(-11) - 5 x 10(-10)M) of a fully biologically active 125 I-GnRH. The treatment, at least, doubled the number of biologically important high affinity GnRH binding sites (Kd's . 7.5 x -10(-11) - 4.5 x 10(-10)M), and changed the binding capacity of some of the binding sites up to three fold, which altered the cooperativity of GnRH-receptor interaction. Thus, the interaction of E2 with GnRH at the level of GnRH receptor is mandatory for the short-term pituitary effect of E2 on LH release in vitro and in vivo

Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs

NARCIS (Netherlands)

Turkstra, J.A.; Staay, van der F.J.; Stockhofe-Zurwieden, N.; Woelders, H.; Meloen, R.H.; Schuurman, T.

2011-01-01

Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide

The use of gonadotrophin-releasing hormone antagonists in polycystic ovarian disease.

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Lubin, V; Charbonnel, B; Bouchard, P

1998-12-01

Polycystic ovarian disease (PCOD) is characterized by anovulation, eventually high luteinizing hormone (LH) levels, with increased LH pulse frequency, and hyperandrogenism. As the aetiology of the disease is still unknown, gonadotrophin-releasing hormone (GnRH) antagonists, competitive inhibitors of GnRH for its receptor, are interesting tools in order to study and treat the role of increased LH levels and pulse frequency in this disease. Their administration provokes a rapid decrease in bioactive and immunoactive LH followed by a slower decrease in follicle-stimulating hormone (FSH). In patients with PCOD, the suppression of gonadotrophin secretion eradicates the symptoms of the disease as long as the treatment lasts. Several authors have suggested that increased plasma LH levels have deleterious effects on the fertility of women with PCOD. Indeed, fewer spontaneous pregnancies with more miscarriages are observed when plasma LH levels are high. Assisted reproduction techniques such as in vitro fertilization (IVF) have provided other clues to the role of the LH secretory pattern in women with PCOD. The number of oocytes retrieved, the fertilization rate and the cleavage rate are lower in PCOD patients undergoing IVF and this is inversely correlated with FSH:LH ratio. These abnormalities are corrected when endogenous secretion of LH is suppressed. On the other hand, implantation and pregnancy rates after IVF are similar to those observed in control women. New GnRH antagonists are devoid of side effects and suppress LH secretion within a few hours without a flare-up effect. This action lasts for 10-100 hours. When GnRH antagonists are associated with i.v. pulsatile GnRH, this combination both suppresses the effect of endogenous GnRH and because of the competition for GnRH receptors restores a normal frequency of LH secretion. We have studied two women with PCOD, administering first 10 mg s.c. every 72 hours for 7 days of the GnRH antagonist Nal-Glu, then adding on

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

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Eide, Per K

2008-11-01

Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

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Gayem İnayet Turgay Çelik

2015-01-01

Full Text Available Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF. Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET program between January 2006 and November 2012. The groups were compared to the patients’ characteristics, controlled ovarian stimulation (COH results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1, and a single protocol was applied to 85 patients (group 2. In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%. A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4% or the clinical pregnancy rates (7.1% versus 10.6%. Conclusion. The combination protocol does not provide additional efficacy.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

Science.gov (United States)

Çelik, Gayem İnayet Turgay; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). The combination protocol does not provide additional efficacy.

Chrono pharmacotherapy: A pulsatile Drug Delivery

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Huma Hameed

2015-01-01

Full Text Available Chronopharmacotherapy refers to a treatment in which controlled drug delivery is achieved according to circadian rhythms of disease by enhancing therapeutic outcomes and minimizing side effects. Colon targeting has gained great importance not only for the treatment of local diseases such as Crohn’s disease, inflammatory bowel disease and ulcerative colitis but also very important in systemic delivery of proteins/peptides, antiasthmatic drugs, antidiabetic agents and antihypertensive drugs, which mostly show their efficacy based on circadian rhythms of the body.Colon drug delivery is one of the difficult approaches to achieve the targeted and desired outcomes through pulsatile drug delivery by avoiding dose dumping.The main reasonbehind the use of pulsatile delivery is provision ofconstant drug release where a zero-order release is notpreferred. Chronopharmacotherapy in colon targeting play its role bymany systems such ascapsular systems, pulsatile system and osmotic systems, which are based on use of rupturable membranes and biodegradable polymers.The objective of this review article is to provide latest knowledge about drugs with chrono-pharmacological behavior entails night time dosing specially to the colon.

Characterization of 12 GnRH peptide agonists - a kinetic perspective.

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Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

2016-01-01

Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

Identification of Genes Enriched in GnRH Neurons by Translating Ribosome Affinity Purification and RNAseq in Mice.

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Burger, Laura L; Vanacker, Charlotte; Phumsatitpong, Chayarndorn; Wagenmaker, Elizabeth R; Wang, Luhong; Olson, David P; Moenter, Suzanne M

2018-04-01

Gonadotropin-releasing hormone (GnRH) neurons are a nexus of fertility regulation. We used translating ribosome affinity purification coupled with RNA sequencing to examine messenger RNAs of GnRH neurons in adult intact and gonadectomized (GDX) male and female mice. GnRH neuron ribosomes were tagged with green fluorescent protein (GFP) and GFP-labeled polysomes isolated by immunoprecipitation, producing one RNA fraction enhanced for GnRH neuron transcripts and one RNA fraction depleted. Complementary DNA libraries were created from each fraction and 50-base, paired-end sequencing done and differential expression (enhanced fraction/depleted fraction) determined with a threshold of >1.5- or <0.66-fold (false discovery rate P ≤ 0.05). A core of ∼840 genes was differentially expressed in GnRH neurons in all treatments, including enrichment for Gnrh1 (∼40-fold), and genes critical for GnRH neuron and/or gonadotrope development. In contrast, non-neuronal transcripts were not enriched or were de-enriched. Several epithelial markers were also enriched, consistent with the olfactory epithelial origins of GnRH neurons. Interestingly, many synaptic transmission pathways were de-enriched, in accordance with relatively low innervation of GnRH neurons. The most striking difference between intact and GDX mice of both sexes was a marked downregulation of genes associated with oxidative phosphorylation and upregulation of glucose transporters in GnRH neurons from GDX mice. This may suggest that GnRH neurons switch to an alternate fuel to increase adenosine triphosphate production in the absence of negative feedback when GnRH release is elevated. Knowledge of the GnRH neuron translatome and its regulation can guide functional studies and can be extended to disease states, such as polycystic ovary syndrome.

Modeling of pulsatile flow-dependent nitric oxide regulation in a realistic microvascular network.

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Wang, Ruofan; Pan, Qing; Kuebler, Wolfgang M; Li, John K-J; Pries, Axel R; Ning, Gangmin

2017-09-01

Hemodynamic pulsatility has been reported to regulate microcirculatory function. To quantitatively assess the impact of flow pulsatility on the microvasculature, a mathematical model was first developed to simulate the regulation of NO production by pulsatile flow in the microcirculation. Shear stress and pressure pulsatility were selected as regulators of endothelial NO production and NO-dependent vessel dilation as feedback to control microvascular hemodynamics. The model was then applied to a real microvascular network of the rat mesentery consisting of 546 microvessels. As compared to steady flow conditions, pulsatile flow increased the average NO concentration in arterioles from 256.8±93.1nM to 274.8±101.1nM (Pflow as compared to steady flow conditions. Network perfusion and flow heterogeneity were improved under pulsatile flow conditions, and vasodilation within the network was more sensitive to heart rate changes than pulse pressure amplitude. The proposed model simulates the role of flow pulsatility in the regulation of a complex microvascular network in terms of NO concentration and hemodynamics under varied physiological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-dose add-back therapy during postoperative GnRH agonist treatment

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Hsiao-Wen Tsai

2016-02-01

Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

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Inaba, T; Tani, H; Gonda, M; Nakagawa, A; Ohmura, M; Mori, J; Torii, R; Tamada, H; Sawada, T

1998-04-01

A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

Mathematical modeling of gonadotropin-releasing hormone signaling.

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Pratap, Amitesh; Garner, Kathryn L; Voliotis, Margaritis; Tsaneva-Atanasova, Krasimira; McArdle, Craig A

2017-07-05

Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are G q -coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Ovulation induction: a mini review.

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Messinis, Ioannis E

2005-10-01

Ovulation induction is the method for treating anovulatory infertility. For patients with hypogonadotrophic hypogonadism, the treatment involves administration of both FSH and LH, while HCG is injected for follicle rupture. Pulsatile GnRH has the same effectiveness as gonadotrophins and the advantage of the low multiple pregnancy rate. In polycystic ovary syndrome (PCOS), the first treatment choice is clomiphene citrate. With this drug, in properly selected patients, the cumulative pregnancy rate approaches that of normal women. Low-dose protocols of FSH are the second line of treatment, effective in inducing monofollicular development. Laparoscopic ovarian drilling can be an alternative but not as a first choice treatment in clomiphene-resistant patients. Other treatments, such as pulsatile GnRH and GnRH agonists, are hardly used today in PCOS. However, in obese women with PCOS, weight loss and exercise should be recommended as the first line of therapy. Newer agents including aromatase inhibitors and insulin sensitizers, although promising, need further evaluation.

Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides.

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Marvel, Miranda; Spicer, Olivia Smith; Wong, Ten-Tsao; Zmora, Nilli; Zohar, Yonathan

2018-04-04

Gonadotropin-releasing hormone (GnRH) is known as a pivotal upstream regulator of reproduction in vertebrates. However, reproduction is not compromised in the hypophysiotropic Gnrh3 knockout line in zebrafish (gnrh3-/-). In order to determine if Gnrh2, the only other Gnrh isoform in zebrafish brains, is compensating for the loss of Gnrh3, we generated a double Gnrh knockout zebrafish line. Surprisingly, the loss of both Gnrh isoforms resulted in no major impact on reproduction, indicating that a compensatory response, outside of the Gnrh system, was evoked. A plethora of factors acting along the reproductive hypothalamus-pituitary axis were evaluated as possible compensators based on neuroanatomical and differential gene expression studies. In addition, we also examined the involvement of feeding factors in the brain as potential compensators for Gnrh2, which has known anorexigenic effects. We found that the double knockout fish exhibited upregulation of several genes in the brain, specifically gonadotropin-inhibitory hormone (gnih), secretogranin 2 (scg2), tachykinin 3a (tac3a), and pituitary adenylate cyclase-activating peptide 1 (pacap1), and downregulation of agouti-related peptide 1 (agrp1), indicating the compensation occurs outside of Gnrh cells and therefore is a non-cell autonomous response to the loss of Gnrh. While the differential expression of gnih and agrp1 in the double knockout line was confined to the periventricular nucleus and hypothalamus, respectively, the upregulation of scg2 corresponded with a broader neuronal redistribution in the lateral hypothalamus and hindbrain. In conclusion, our results demonstrate the existence of a redundant reproductive regulatory system that comes into play when Gnrh2 and Gnrh3 are lost.

Expression of the GnRH and GnRH receptor (GnRH-R) genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland of anestrous and luteal phase ewes.

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Ciechanowska, Magdalena; Lapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2008-11-01

Data exists showing that seasonal changes in the innervations of GnRH cells in the hypothalamus and functions of some neural systems affecting GnRH neurons are associated with GnRH release in ewes. Consequently, we put the question as to how the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland is reflected with LH secretion in anestrous and luteal phase ewes. Analysis of GnRH gene expression by RT-PCR in anestrous ewes indicated comparable levels of GnRH mRNA in the preoptic area, anterior and ventromedial hypothalamus. GnRH-R mRNA at different concentrations was found throughout the preoptic area, anterior and ventromedial hypothalamus, stalk/median eminence and in the anterior pituitary gland. The highest GnRH-R mRNA levels were detected in the stalk/median eminence and in the anterior pituitary gland. During the luteal phase of the estrous cycle in ewes, the levels of GnRH mRNA and GnRH-R mRNA in all structures were significantly higher than in anestrous ewes. Also LH concentrations in blood plasma of luteal phase ewes were significantly higher than those of anestrous ewes. In conclusion, results from this study suggest that low expression of the GnRH and GnRH-R genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland, amongst others, may be responsible for a decrease in LH secretion and the anovulatory state in ewes during the long photoperiod.

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

Science.gov (United States)

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

GnRH Antagonist/Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing In Vitro Fertilization

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Robab Davar

2010-09-01

Conclusion: The addition of letrozole to the GnRH antagonist for poor responders does not improve the outcome of assisted reproductive technology cycles. The MF protocol remains the most appropriate protocol in poor responders.

Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.

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Nakata, Daisuke; Masaki, Tsuneo; Tanaka, Akira; Yoshimatsu, Mie; Akinaga, Yumiko; Asada, Mari; Sasada, Reiko; Takeyama, Michiyasu; Miwa, Kazuhiro; Watanabe, Tatsuya; Kusaka, Masami

2014-01-15

TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH antagonist TAK-013. TAK-385 possesses higher affinity and more potent antagonistic activity for human and monkey GnRH receptors compared with TAK-013. Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them difficult to evaluate in rodent models. Here we report the human GnRH receptor knock-in mouse as a humanized model to investigate pharmacological properties of these compounds on gonadal function. Twice-daily oral administration of TAK-013 (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in male knock-in mice but not in male wild-type mice, demonstrating the validity of this model to evaluate antagonists for the human GnRH receptor. The same dose of TAK-385 also reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone-dependent diseases including endometriosis, uterine fibroids and prostate cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

KAUST Repository

Zhang, Xiaomei; Bocca, Silvina Maria; Franchi, Anahí ; Anderson, Sandra; Kaur, Mandeep; Bajic, Vladimir B.; Oehninger, Sergio Carlos

2010-01-01

were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues

Selective enhancement of main olfactory input to the medial amygdala by GnRH.

Science.gov (United States)

Blake, Camille Bond; Meredith, Michael

2010-03-04

In male hamsters mating behavior is dependent on chemosensory input from the main olfactory and vomeronasal systems, whose central pathways contain cell bodies and fibers of gonadotropin-releasing hormone (GnRH) neurons. In sexually naive males, vomeronasal organ removal (VNX), but not main olfactory lesions, impairs mating behavior. Intracerebroventricular (i.c.v.)-GnRH restores mating in sexually naive VNX males and enhances medial amygdala (Me) immediate-early gene activation by chemosensory stimulation. In sexually experienced males, VNX does not impair mating and i.c.v.-GnRH suppresses Me activation. Thus, the main olfactory system is sufficient for mating in experienced-VNX males, but not in naive-VNX males. We investigated the possibility that GnRH enhances main olfactory input to the amygdala in naive-VNX males using i.c.v.-GnRH and pharmacological stimulation (bicuculline/D,L-homocysteic acid mixture) of the main olfactory bulb (MOB). In sexually naive intact males there was a robust increase of Fos protein expression in the anteroventral medial amygdala (MeAv) with MOB stimulation, but no effect of GnRH. There was no effect of stimulation or GnRH in posterodorsal medial amygdala (MePd). In naive-VNX animals, GnRH increased Fos in MeAv and MePv. Only combined MOB stimulation and i.c.v.-GnRH produced a significant increase in Fos in the dorsal (reproduction-related) portion of MeP (MePd). When the animals were sexually experienced before VNX, a condition in which GnRH does not enhance mating, i.c.v.-GnRH combined with MOB stimulation suppressed Fos expression in MePd. This suggests a more selective effect of GnRH on olfactory input in MePd than elsewhere in medial amygdala of VNX males. 2009 Elsevier B.V. All rights reserved.

A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

Science.gov (United States)

Hoffmann, Hanne M; Mellon, Pamela L

2016-01-01

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 ( Vax1 ) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1 flox mice and crossed them with Gnrh cre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1 flox/flox :GnRH cre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1 flox/flox :GnRH cre :RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and

Pulsatile pipe flow transition: Flow waveform effects

Science.gov (United States)

Brindise, Melissa C.; Vlachos, Pavlos P.

2018-01-01

Although transition is known to exist in various hemodynamic environments, the mechanisms that govern this flow regime and their subsequent effects on biological parameters are not well understood. Previous studies have investigated transition in pulsatile pipe flow using non-physiological sinusoidal waveforms at various Womersley numbers but have produced conflicting results, and multiple input waveform shapes have yet to be explored. In this work, we investigate the effect of the input pulsatile waveform shape on the mechanisms that drive the onset and development of transition using particle image velocimetry, three pulsatile waveforms, and six mean Reynolds numbers. The turbulent kinetic energy budget including dissipation rate, production, and pressure diffusion was computed. The results show that the waveform with a longer deceleration phase duration induced the earliest onset of transition, while the waveform with a longer acceleration period delayed the onset of transition. In accord with the findings of prior studies, for all test cases, turbulence was observed to be produced at the wall and either dissipated or redistributed into the core flow by pressure waves, depending on the mean Reynolds number. Turbulent production increased with increasing temporal velocity gradients until an asymptotic limit was reached. The turbulence dissipation rate was shown to be independent of mean Reynolds number, but a relationship between the temporal gradients of the input velocity waveform and the rate of turbulence dissipation was found. In general, these results demonstrated that the shape of the input pulsatile waveform directly affected the onset and development of transition.

The Use of a Combined Regimen of GnRH Agonist Plus a Low-Dose Oral Contraceptive Improves the Spontaneous Pulsatile LH Secretory Characteristics in Patients with Polycycstic Ovary Disease After Discontinuation of Treatment

OpenAIRE

Genazzani, Alessandro D.; Battaglia, Cesare; Gamba, Ombretta; Petraglia, Felice; Malavasi, Barbara; Genazzani, Andrea R.

2000-01-01

Purpose: The fertility rate in women with polycystic ovarydisease (PCOD) is influenced by the type of treatmentreceived. The present study evaluated the possiblecorrelation between treatment and pulsatile release ofgonadotropins.

Basal testosterone concentrations after the application of a slow-release GnRH agonist implant are associated with a loss of response to buserelin, a short-term GnRH agonist, in the tom cat.

Science.gov (United States)

Goericke-Pesch, Sandra; Georgiev, Plamen; Fasulkov, Ivan; Vodenicharov, Angel; Wehrend, Axel

2013-07-01

Slow-release GnRH agonist implants are considered an effective, reversible alternative to surgical castration in male tom cats. Individual differences exist regarding the onset of efficacy and might be delayed in some animals. Single measurements of testosterone (T) might result in basal concentrations also in intact male cats. Consequently, GnRH stimulation tests are performed to measure T increase in intact animals and to differentiate castrated from intact male cats. In this study, five tom cats were treated with a 4.7-mg deslorelin implant and GnRH stimulation tests using buserelin were performed before treatment and at 4-week intervals afterward until Week 20. After the last test in Week 20 all animals were castrated. Four of five animals had basal T after 4 weeks and-in contrast to pretreatment-application of buserelin did not result in any further T increase. In one animal, T was low after implant insertion, but not basal; however, a GnRH stimulation test induced a slight increase of T in Week 8 and 16 only and no response in Weeks 4, 12, and 20. Testicular volume was significantly decreased and penile spines disappeared in all cats. Testicular histology showed mixed atrophy, but also fully elongated spermatids in three of five male cats making infertility questionable. Because of the loss of the stimulatory effect of short-term GnRH application (buserelin), it can be assumed that long-term GnRH agonists also act by some mechanisms of downregulation of pituitary GnRH receptors in the tom cat. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of Acute Resistance Exercise on Carotid Artery Stiffness and Cerebral Blood Flow Pulsatility

Directory of Open Access Journals (Sweden)

Wesley K Lefferts

2014-03-01

Full Text Available Arterial stiffness is associated with cerebral flow pulsatility. Arterial stiffness increases following acute resistance exercise (RE. Whether this acute RE-induced vascular stiffening affects cerebral pulsatility remains unknown. Purpose: To investigate the effects of acute RE on common carotid artery (CCA stiffness and cerebral blood flow velocity (CBFv pulsatility. Methods: Eighteen healthy men (22 ± 1 yr; 23.7 ± 0.5 kg∙m-2 underwent acute RE (5 sets, 5-RM bench press, 5 sets 10-RM bicep curls with 90 s rest intervals or a time control condition (seated rest in a randomized order. CCA stiffness (β-stiffness, Elastic Modulus (Ep and hemodynamics (pulsatility index, forward wave intensity and reflected wave intensity were assessed using a combination of Doppler ultrasound, wave intensity analysis and applanation tonometry at baseline and 3 times post-RE. CBFv pulsatility index was measured with transcranial Doppler at the middle cerebral artery (MCA. Results: CCA β-stiffness, Ep and CCA pulse pressure significantly increased post-RE and remained elevated throughout post-testing (p 0.05. There were significant increases in forward wave intensity post-RE (p0.05. Conclusion: Although acute RE increases CCA stiffness and pressure pulsatility, it may not affect CCA or MCA flow pulsatility. Increases in pressure pulsatility may be due to increased forward wave intensity and not pressure from wave reflections.

Impaired crosstalk between pulsatile insulin and glucagon secretion in prediabetic individuals

DEFF Research Database (Denmark)

Rohrer, Stefan; Menge, Björn A; Grüber, Lena

2012-01-01

Postprandial hyperglucagonemia is frequently found in patients with diabetes. Recently, a loss of the inverse relationship between pulsatile insulin and glucagon secretion has been reported in patients with type 2 diabetes. The crosstalk between pulsatile islet hormone secretion in prediabetic...

Photoaffinity labeling of pituitary GnRH receptors: significance of the position of photolabel on the ligand

International Nuclear Information System (INIS)

Nikolics, K.; Szonyi, E.; Ramachandran, J.

1988-01-01

Photoreactive derivatives of GnRH and its analogues were prepared by incorporation of the 2-nitro-4(5)-azidophenylsulfenyl [2,4(5)-NAPS] group into amino acid residues at position 1, 3, 6, or 8 of the decapeptide sequence. The modification of Trp 3 by the 2,4-NAPS group led to a complete loss of the luteinizing hormone (LH) releasing as well as LH-release-inhibiting activity of the peptide. The [D-Lys(2,4-NAPS)] 6 analog was a very potent agonist that, after covalent attachment by photoaffinity labeling, caused prolonged LH secretion at a submaximal rate. [Orn(2,4-NAPS)] 8 -GnRH, a full agonist with a relative potency of 7% of GnRH, after photoaffinity labeling caused prolonged maximal LH release from cultured pituitary cells. In contrast, [Orn(2,5-NAPS)] 8 -GnRH, although being equipotent with the 2,4-NAPS isomer in terms of LH releasing ability, was unable to cause prolonged LH release after photoaffinity labeling. Thus, [Orn(2,4-NAPS)] 8 GnRH is very effective photolabeling ligand of the functionally significant pituitary GnRH receptor. Based on this compound, a pituitary peptidase resistant derivative, D-Phe 6 , [Orn(2,4-NAPS)] 8 -GnRH-(1-9)-ethylamide, was synthesized. This derivative showed high-affinity binding to pituitary membranes with a K/sub d/ comparable to those of other GnRH analogues. A radioiodinated form of this peptide was used for pituitary GnRH-receptor labeling. This derivative labeled 59- and 57-kDa proteins in rat and 58- and 56-kDa proteins in bovine pituitary membrane preparations, respectively. This peptide also labeled pituitary GnRH receptors in the solubilized state and therefore appears to be a suitable ligand for the isolation and further characterization of the receptor

Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

Science.gov (United States)

Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2011-01-01

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

Cerebral blood flow and intracranial pulsatility studied with MRI: measurement, physiological and pathophysiological aspects

International Nuclear Information System (INIS)

Waahlin, Anders

2012-01-01

During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects.Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile

Cerebral blood flow and intracranial pulsatility studied with MRI: measurement, physiological and pathophysiological aspects

Energy Technology Data Exchange (ETDEWEB)

Waahlin, Anders

2012-07-01

During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects.Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile

Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

Science.gov (United States)

Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

2017-01-01

Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis.

Science.gov (United States)

Tranoulis, Anastasios; Laios, Alexandros; Pampanos, Andreas; Yannoukakos, Drakoulis; Loutradis, Dimitrios; Michala, Lina

2018-04-01

To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA). Systematic review and meta-analysis. Not applicable. A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA. None. Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR). multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI). Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST. The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pulsatile versus steady infusions for hepatic artery chemotherapy

International Nuclear Information System (INIS)

Kim, E.E.; Haynie, T.P.; Wright, K.C.; Chaynsangavej, C.; Gianturco, C.; Lamki, L.; Wallace, S.

1984-01-01

Hepatic artery chemotherapy for unresectable liver tumors requires an even distribution of the drugs in the tumor or vascular bed. This cannot be determined angiographically because the drugs are infused at a much lower rate than the contrast media. It is easy, however, to determine the quality of the perfusion by injecting a small volume of Tc-99m MAA in one of the side ports while chemotherapeutic agent is being infused at the same rate. Usually this shows a uniform, satisfactory distribution of isotope. Occasionally, however, some areas fail to receive Tc-99m in spite of what appears to be a good position of the catheter tip. Since ''streaming'' of the infused drugs has been blamed for their uneven distribution, the authors decided to compare the usual steady flow infusions with infusions made pulsatile by the addition of a pulsing device (Gianturco Pump) attached to the infusion tubing. Eighty-three patients were studied with steady as well as pulsatile infusions. In 16 of these patients the perfusion pattern was definitely changed by the pulsatile infusion. In one patient the pulsatile mode resulted in an unwanted gastric perfusion. In 5 patients the distribution was improved in one hepatic lobe and in 10 patients it was improved in both lobes. These results show that hepatic artery perfusions can occasionally be improved by pulsing the infusate. However, pulsing can produce the unwanted perfusion of extra-hepatic areas

Investigation of the pulsatile pipe flow

Czech Academy of Sciences Publication Activity Database

Adamec, J.; Nožička, J.; Kořenář, Josef

2000-01-01

Roč. 18, č. 2 (2000), s. 17-22 ISSN 0392-8764 Institutional research plan: CEZ:AV0Z2060917 Keywords : pulsatile flow * laminar-turbulent transition * reynolds normal stress Subject RIV: BK - Fluid Dynamics

Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI.

Science.gov (United States)

Esinler, I

2014-01-01

To compare the performance of microdose flare-up (MF) and flexible-multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients.

Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist

DEFF Research Database (Denmark)

Al Humaidan, Peter Samir Heskjær; Bungum, L; Bungum, M

2006-01-01

Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI p......RHa supplemented with 1500 IU HCG 35 h later (group 3) seems to secure a normal luteal phase and a normal clinical pregnancy outcome....

GnRH Neuron Activity and Pituitary Response in Estradiol-Induced vs Proestrous Luteinizing Hormone Surges in Female Mice.

Science.gov (United States)

Silveira, Marina A; Burger, Laura L; DeFazio, R Anthony; Wagenmaker, Elizabeth R; Moenter, Suzanne M

2017-02-01

During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons. Copyright © 2017 by the Endocrine Society.

Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

Science.gov (United States)

Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

2008-01-01

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

Science.gov (United States)

Herde, Michel K; Herbison, Allan E

2015-11-01

GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

Treatment of idiopathic hypogonadotropic hypogonadism in men with luteinizing hormone-releasing hormone: a comparison of treatment with daily injections and with the pulsatile infusion pump.

Science.gov (United States)

Shargil, A A

1987-03-01

Thirty husbands in childless couples, aged 24 to 35 years, were treated with luteinizing hormone-releasing hormone (LH-RH) for idiopathic hypogonadotropic hypogonadism (IHH) of peripubertal (incomplete) type. They were azoospermic or oligospermic, with less than 1.5 X 10(6)/ml nonmotile spermatozoa. The diagnosis of IHH was based on clinical and laboratory features and testicular biopsy specimen study and was further supported by results of stimulation tests and gonadotropin-releasing hormone (GnRH) test. Two treatment modalities were used: subcutaneous injections of 500 micrograms LH-RH twice daily; and perpetual subcutaneous injection, via portable infusion pump, of 25 ng/kg LH-RH, at 90-minute intervals. Two patients required a short second period of pulsatile treatment to cause a second pregnancy of their spouses. The pump proved to yield better results, compared with intermittent injections, in respect to endocrine responses, spermatogenesis, and fertility capacity. Normal levels of luteinizing hormone and follicle-stimulating hormone were reached in 2 to 3 weeks and normal testosterone levels in 8 to 10 weeks from the start of treatment. Sperm counts rose to greater than 60 X 10(6)/ml viable spermatozoa with less than 15% of abnormal forms in 3 to 5 months, and the wives conceived. Of a total of 18 deliveries of healthy infants, 12 offspring were identified genetically with their fathers. Four women were still pregnant at the conclusion of the study. The pump was well tolerated, without special operational problems to the patients. Pulsatile treatment is therefore recommended in the treatment of well-diagnosed and carefully selected cases of incomplete IHH.

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

KAUST Repository

Zhang, Xiaomei

2010-03-04

We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Directory of Open Access Journals (Sweden)

Guo S

2017-03-01

Full Text Available Song Guo,1,* Xiaowei Lu,1,* Ruihuan Gu,2 Di Zhang,3 Yijuan Sun,2 Yun Feng1 1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Jinan Military General Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.Methods: Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each. The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR.Results: The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05. However, the average live litter

Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes

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Menge, Björn A; Grüber, Lena; Jørgensen, Signe M

2011-01-01

In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known.......In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known....

GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient-friendly assisted reproductive technology.

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Tur-Kaspa, Ilan; Ezcurra, Diego

2009-10-01

Gonadotropin-releasing hormone (GnRH) analogues are used routinely to prevent a premature luteinizing hormone (LH) surge in women undergoing assisted reproductive technology (ART) treatments. In contrast to GnRH agonists, antagonists produce rapid and reversible suppression of LH with no initial flare effect. To review the role of cetrorelix, the first GnRH antagonist approved for the prevention of premature LH surges during controlled ovarian stimulation in modern ART. A review of published literature on cetrorelix. Both multiple- and single-dose cetrorelix protocols were shown to be at least as effective as long GnRH agonist regimens for pituitary suppression in Phase II/III clinical trials. Furthermore, cetrorelix co-treatment resulted in similar live birth rates but a shorter duration of gonadotropin stimulation, a lower total gonadotropin dose requirement and lower incidence of ovarian hyperstimulation syndrome compared with long agonist regimens. A single-dose cetrorelix protocol further decreased the number of injections required. Preliminary studies have also produced promising data on the use of cetrorelix in modified ART protocols, such as frozen embryo transfer and donor oocyte recipient cycles. Cetrorelix offers a potential therapeutic alternative to GnRH agonists during controlled ovarian stimulation and has become an integral part of modern, patient-friendly reproductive medicine.

Glucosensing by GnRH Neurons: Inhibition by Androgens and Involvement of AMP-Activated Protein Kinase

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Roland, Alison V.

2011-01-01

GnRH neurons integrate steroidal and metabolic cues to regulate fertility centrally. Central glucoprivation reduces LH secretion, which is governed by GnRH release, suggesting GnRH neuron activity is modulated by glucose availability. Here we tested whether GnRH neurons can sense changes in extracellular glucose, and whether glucosensing is altered by the steroids dihydrotestosterone (DHT) and/or estradiol (E). Extracellular recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice ± DHT and/or E implants. Firing rate was reduced by a switch from 4.5 to 0.2 mm glucose in cells from OVX, OVX+E, and OVX+DHT+E mice, but not OVX+DHT mice. This suggests that androgens reduce the sensitivity of GnRH neurons to changes in extracellular glucose, but E mitigates this effect. Next we investigated potential mechanisms. In the presence of the ATP-sensitive potassium channel antagonist tolbutamide, glucosensing persisted. In contrast, glucosensing was attenuated in the presence of compound C, an antagonist of AMP-activated protein kinase (AMPK), suggesting a role for AMPK in glucosensing. The AMPK activator N1-(b-d-ribofuranosyl)-5-aminoimidazole-4-carboxamide (AICAR) mimicked the effect of low glucose and was less effective in cells from DHT-treated mice. The effect of DHT to diminish responses to low glucose and AICAR was abolished by blockade of fast synaptic transmission. Both AICAR and low glucose activated a current with a reversal potential near −50 mV, suggesting a nonspecific cation current. These studies indicate that glucosensing is one mechanism by which GnRH neurons sense fuel availability and point to a novel role for AMPK in the central regulation of fertility. PMID:21393446

Dynamic GnRH and hCG testing

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Bang, A. Kirstine; Nordkap, Loa; Almstrup, Kristian

2017-01-01

OBJECTIVE: Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after Gn...... influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic-pituitary-gonadal axis. METHODS: Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC-MS/MS. RESULTS......: For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7-67.6 nmol/L) during hCG testing. None of the polymorphisms had any major...

Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders

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Hemchand K Prasad

2012-01-01

Full Text Available Context: Gonadotrophin releasing hormone (GnRH stimulation test is pivotal in the assessment of children with pubertal disorders. However, lack of availability and high cost often result in the test falling into disfavor. We routinely use the GnRH analogue stimulation test as an alternative at our center. Aim: To present the data on children with endocrine disorders who underwent GnRH agonist stimulation test in pediatric endocrine clinic of a tertiary care referral hospital. Setting and Design: Pediatric endocrine clinic of a tertiary care referral hospital. Retrospective analysis of case records. Materials and Methods: The details pertaining to clinical and radiological parameters and hormonal tests were retrieved from case records of 15 children who underwent GnRH agonist stimulation test from May 2010 to April 2011. Results: Indications for testing with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious puberty, assessment of hormonal suppression in treatment of precocious puberty and micropenis in two, nine, three and one cases, respectively. The results of the test and clinical and radiological parameters were in concordance. The test was also crucial in diagnosing the onset of central precocious puberty in two children with congenital adrenal hyperplasia. Conclusion: GnRH agonist test is a convenient, safe test that can be performed on an out-patient basis and can help the clinicians in the correct diagnosis and appropriate treatment of various puberty-related disorders.

Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio).

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Zhao, Yali; Singh, Chanpreet; Prober, David A; Wayne, Nancy L

2016-10-01

GnRH neurons integrate internal and external cues to control sexual maturation and fertility. Homeostasis of energy balance and food intake correlates strongly with the status of reproduction. Neuropeptides secreted by the hypothalamus involved in modulating energy balance and feeding may play additional roles in the regulation of reproduction. Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing. There is a growing body of evidence indicating that Hcrt/orexin (Hcrt) modulates reproduction through interacting with the hypothalamo-pituitary-gonadal axis in mammals. To explore potential morphological and functional interactions between the GnRH and Hcrt neuronal systems, we employed a variety of experimental approaches including confocal imaging, immunohistochemistry, and electrophysiology in transgenic zebrafish, in which fluorescent proteins are genetically expressed in GnRH3 and Hcrt neurons. Our imaging data revealed close apposition and direct connection between GnRH3 and Hcrt neuronal systems in the hypothalamus during larval development through adulthood. Furthermore, the Hcrt receptor (HcrtR) is expressed in GnRH3 neurons. Electrophysiological data revealed a reversible inhibitory effect of Hcrt on GnRH3 neuron electrical activity, which was blocked by the HcrtR antagonist almorexant. In addition, Hcrt had no effect on the electrical activity of GnRH3 neurons in the HcrtR null mutant zebrafish (HcrtR -/- ). Our findings demonstrate a close anatomical and functional relationship between Hcrt and GnRH neuronal systems in zebrafish. It is the first demonstration of a link between neuronal circuits controlling sleeping/arousal/feeding and reproduction in zebrafish, an important animal model for investigating the molecular genetics of development.

Social Crowding during Development Causes Changes in GnRH1 DNA Methylation.

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Alvarado, Sebastian G; Lenkov, Kapa; Williams, Blake; Fernald, Russell D

2015-01-01

Gestational and developmental cues have important consequences for long-term health, behavior and adaptation to the environment. In addition, social stressors cause plastic molecular changes in the brain that underlie unique behavioral phenotypes that also modulate fitness. In the adult African cichlid, Astatotilapia burtoni, growth and social status of males are both directly regulated by social interactions in a dynamic social environment, which causes a suite of plastic changes in circuits, cells and gene transcription in the brain. We hypothesized that a possible mechanism underlying some molecular changes might be DNA methylation, a reversible modification made to cytosine nucleotides that is known to regulate gene function. Here we asked whether changes in DNA methylation of the GnRH1 gene, the central regulator of the reproductive axis, were altered during development of A. burtoni. We measured changes in methylation state of the GnRH1 gene during normal development and following the gestational and developmental stress of social crowding. We found differential DNA methylation within developing juveniles between 14-, 28- and 42-day-old. Following gestational crowding of mouth brooding mothers, we saw differential methylation and transcription of GnRH1 in their offspring. Taken together, our data provides evidence for social control of GnRH1 developmental responses to gestational cues through DNA methylation.

Kisspeptin and LH pulsatile temporal coupling in PCOS patients.

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Katulski, Krzysztof; Podfigurna, Agnieszka; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Alessandro D

2018-05-04

To evaluate the temporal coupling between spontaneous kisspeptin and luteinizing hormone (LH) pulsatile releases in polycystic ovary syndrome (PCOS) patients. We examined 71 patients diagnosed with PCOS. A 2 h pulsatility study was performed to evaluate serum kisspeptin and LH pulse frequency and concentration, sampled every 10 min; baseline follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), cortisol, 17-hydroksy-progesterone (17OHP), testosterone (T), free testosterone index (FTI, and insulin levels were also measured. Detect and Specific Concordance (SC) algorithms were used to evaluate the temporal coupling associations between spontaneous episodic secretion of kisspeptin and LH. All PCOS patients demonstrated LH and kisspeptin pulsatile secretions. When the SC index was calculated across the sample of PCOS patients (n = 71), no temporal coupling was observed between kisspeptin and LH pulses. When PCOS patients were subdivided according to their menstrual cyclicity, oligomenorrheic patients demonstrated elevated kisspeptin pulse frequency. Additionally, the SC index reveled a temporal coupling between kisspeptin and LH secretory peaks only in eumenorrheic patients (n = 30, intermenstrual interval PCOS patients (intermenstrual interval > 45 days) did not demonstrate temporal coupling between kisspeptin and LH secretory peaks. The study of the endogenous kisspeptin and LH pulsatile release revealed the temporal coupling of kisspeptin with LH secretory pulses only in eumenorrheic. This data supports the hypothesis that neuroendocrine impairments in PCOS affect the coupling of kisspeptin with LH pulses and potentially worsen as the disease progresses, becoming unequivocally evident in oligomenorrheic PCOS patients.

Heat Transfer to Pulsatile Slip Flow in a Porous Channel Filled With ...

African Journals Online (AJOL)

This paper investigate the effect of slip on the hydromagnetic pulsatile flow through a porous channel filled with saturated porous medium with time dependent boundary condition on the heated wall. Based on the pulsatile flow nature, the dimensionless flow governing equations are resolved to harmonic and non-harmonic ...

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

International Nuclear Information System (INIS)

Paolisso, G.; Scheen, A.J.; Luyckx, A.S.; Lefebvre, P.J.

1987-01-01

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin, basal insulin secretion was replaced by a continuous insulin infusion, and glucagon was infused intravenously in two conditions at random: either continuously or intermittently. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3- 3 H]glucose infusion allowed the authors to study glucose turnover. While basal plasma glucagon levels were similar in both conditions, they plateaued at 189 +/- 38 pg ml -1 during continuous infusion and varied between 95 and 501 pg x ml -1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion 1) initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, 2) did not prevent the so-called evanescent effect of glucagon on blood glucose, and 3) after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucanemia in normal man fails to increase hepatic glucose production

Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

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Marshall, P E; Goldsmith, P C

1980-07-14

The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

Cerebrovascular blood oxygenation level dependent pulsatility at baseline and following acute exercise among healthy adolescents.

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Theyers, Athena E; Goldstein, Benjamin I; Metcalfe, Arron Ws; Robertson, Andrew D; MacIntosh, Bradley J

2018-01-01

Arterial stiffness is linked to cerebral small vessel damage and neurodegeneration, but barriers to accessing deep cerebrovascular anatomy limit our ability to assess the brain. This study describes an adaptation of a cardiac-related scrubbing method as a means of generating blood oxygenation level-dependent pulsatility maps based on the cardiac cycle. We examine BOLD pulsatility at rest, based on the non-parametric deviation from null metric, as well as changes following acute physiological stress from 20 min of moderate-intensity cycling in 45 healthy adolescents. We evaluate the influence of repetition time (TR) and echo time (TE) using simulated and multi-echo empirical data, respectively. There were tissue-specific and voxel-wise BOLD pulsatility decreases 20 min following exercise cessation. BOLD pulsatility detection was comparable over a range of TR and TE values when scan volumes were kept constant; however, short TRs (≤500 ms) and TEs (∼14 ms) acquisitions would yield the most efficient detection. Results suggest cardiac-related BOLD pulsatility may represent a robust and easily adopted method of mapping cerebrovascular pulsatility with voxel-wise resolution.

In silico and in situ characterization of the zebrafish (Danio rerio gnrh3 (sGnRH gene

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Husebye Harald

2002-08-01

Full Text Available Abstract Background Gonadotropin releasing hormone (GnRH is responsible for stimulation of gonadotropic hormone (GtH in the hypothalamus-pituitary-gonadal axis (HPG. The regulatory mechanisms responsible for brain specificity make the promoter attractive for in silico analysis and reporter gene studies in zebrafish (Danio rerio. Results We have characterized a zebrafish [Trp7, Leu8] or salmon (s GnRH variant, gnrh3. The gene includes a 1.6 Kb upstream regulatory region and displays the conserved structure of 4 exons and 3 introns, as seen in other species. An in silico defined enhancer at -976 in the zebrafish promoter, containing adjacent binding sites for Oct-1, CREB and Sp1, was predicted in 2 mammalian and 5 teleost GnRH promoters. Reporter gene studies confirmed the importance of this enhancer for cell specific expression in zebrafish. Interestingly the promoter of human GnRH-I, known as mammalian GnRH (mGnRH, was shown capable of driving cell specific reporter gene expression in transgenic zebrafish. Conclusions The characterized zebrafish Gnrh3 decapeptide exhibits complete homology to the Atlantic salmon (Salmo salar GnRH-III variant. In silico analysis of mammalian and teleost GnRH promoters revealed a conserved enhancer possessing binding sites for Oct-1, CREB and Sp1. Transgenic and transient reporter gene expression in zebrafish larvae, confirmed the importance of the in silico defined zebrafish enhancer at -976. The capability of the human GnRH-I promoter of directing cell specific reporter gene expression in zebrafish supports orthology between GnRH-I and GnRH-III.

In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line.

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Pal, Lubna; Chu, Hsiao-Pai; Shu, Jun; Topalli, Ilir; Santoro, Nanette; Karkanias, George

2007-10-01

To evaluate for direct toxic effects of high glucose concentrations on cellular physiology in GnRH secreting immortalized GT1-1 neurons. Prospective experimental design. In vitro experimental model using a cell culture system. GT1-1 cells were cultured in replicates in media with two different glucose concentrations (450 mg/dL and 100 mg/dL, respectively) for varying time intervals (24, 48, and 72 hours). Effects of glucose concentrations on GnRH secretion by the GT1-1 neurons were evaluated using a static culture model. Cell viability, cellular apoptosis, and cell cycle events in GT1-1 neurons maintained in two different glucose concentrations were assessed by flow cytometry (fluorescence-activated cell sorter) using Annexin V-PI staining. Adverse influences of high glucose concentrations on GnRH secretion and cell viability were noted in cultures maintained in high glucose concentration (450 mg/dL) culture medium for varying time intervals. A significantly higher percentage of cells maintained in high glucose concentration medium demonstrated evidence of apoptosis by a fluorescence-activated cell sorter. We provide in vitro evidence of glucose-induced cellular toxicity in GnRH secreting GT1-1 neurons. Significant alterations in GnRH secretion, reduced cell viability, and a higher percentage of apoptotic cells were observed in GT1-1 cells maintained in high (450 mg/dL) compared with low (100 mg/dL) glucose concentration culture medium.

Efficiency of fixed-time artificial insemination using a progesterone device combined with GnRH or estradiol benzoate in Nellore heifers

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Vinícius Antônio Pelissari Poncio

2015-10-01

Full Text Available he use of estrogens in artificial insemination protocols for cattle is the least expensive and most efficient method currently available. However, the trend to prohibit the use of estrogens for this purpose has made it necessary to find alternatives that replace estrogens without compromising the reproductive performance of the animals. The objective of this study was to evaluate conception rates in Bos indicus beef heifers treated with a progesterone device (P4 combined with GnRH or an estradiol ester. On day 0, pubertal Nellore heifers (n = 100 received an intravaginal device containing 1 g P4 and were randomly divided into two groups. The GnRH group (n = 49 received an intramuscular injection of 100 µg GnRH, while the E2 group (n = 51 received 2 mg estradiol benzoate (EB. The P4 device was removed after 5 (GnRH group or 8 days (E2 group, followed by an injection of 125 µg of the PGF2α, analog cloprostenol. On that occasion, the E2 group received an additional injection of 300 IU eCG. Twenty-four hours later, the GnRH group received a second injection of 125 µg cloprostenol, while the E2 group received 1 mg EB. The heifers were inseminated 72 (GnRH group or 54 hours (E2 group after removal of the P4 device. At the time of insemination, the GnRH group received additionally an injection of 100 µg GnRH. Estrus was monitored during the period of cloprostenol injection until the time of artificial insemination and pregnancy was diagnosed 40 days after insemination by transrectal ultrasonography. The data were analyzed by Fisher’s exact test. The pregnancy rate was 38.8% and 31.4% in the GnRH and E2 groups, respectively (P>0.05. The ovarian condition of the heifers (estrus or anestrus tended to influence (P=0.07 pregnancy rates in the GnRH group, but not in the E2 group. At the time of artificial insemination, 33.3% of heifers in the GnRH group showed signs of estrus versus 88.2% in the E2 group (P<0.05. However, the time of estrus

Effects of acute aerobic exercise on arterial stiffness and cerebrovascular pulsatility in adults with and without hypertension.

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Lefferts, Wesley K; DeBlois, Jacob P; Receno, Candace N; Barreira, Tiago V; Brutsaert, Tom D; Carhart, Robert L; Heffernan, Kevin S

2018-04-19

Stiffer central arteries, as seen in hypertension (HTN), foster transmission of pulsatile hemodynamics into fragile cerebral vessels. Aerobic exercise is recommended for adults with HTN, but its effects on arterial stiffness and pulsatility in this group are unclear. This study sought to investigate the effect of acute aerobic exercise on arterial stiffness and cerebrovascular pulsatility in 30 adults with treated HTN and 30 age, sex, and BMI-matched adults without HTN (56 ± 6 years, BMI 28.2 ± 2.9 kg/m; 28 women). Patients underwent hemodynamic measures before/after 30-min cycling (≈55% peak oxygen consumption). Aortic stiffness was measured using carotid-femoral pulse wave velocity, and carotid artery stiffness was assessed with β-stiffness via ultrasound. Aortic/carotid pulse pressure (aortic via radial generalized transfer function) was measured by tonometry and calibrated to brachial mean pressure and diastolic pressure. Carotid/middle cerebral artery (MCA) blood velocity pulsatility indices were measured using Doppler. Carotid wave intensity analysis was used to derive forward wave intensity (W1). Exercise impacted hemodynamics similarly in HTN compared to no-HTN. Carotid-femoral pulse wave velocity, MCA pulsatility index, carotid pulsatility index, and W1 increased similarly after exercise in both groups (P < 0.05). Carotid pulse pressure and β-stiffness were unaltered after exercise. Postexercise changes in W1 were positively associated with carotid pulsatility index, which was further associated with MCA pulsatility index. These data suggest adults with treated HTN experience similar increases in aortic stiffness and cerebrovascular hemodynamic pulsatility during early recovery from acute aerobic exercise as their counterparts without HTN.

The pituitary-gonadal axis in healthy female dogs and bitches with gynecological disorders

NARCIS (Netherlands)

Buijtels, J.J.C.W.M.

2011-01-01

The pituitary gland produces and secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in a pulsatile fashion, induced by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Different cells in the ovary are capable of secreting estradiol, testosterone and

Non-invasive assessment of pulsatile intracranial pressure with phase-contrast magnetic resonance imaging.

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Geir Ringstad

Full Text Available Invasive monitoring of pulsatile intracranial pressure can accurately predict shunt response in patients with idiopathic normal pressure hydrocephalus, but may potentially cause complications such as bleeding and infection. We tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of "true" normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43. Pulse pressure gradients were also similar in patients and healthy controls (P = .26, and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97. Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate

Progesterone treatment inhibits and dihydrotestosterone (DHT) treatment potentiates voltage-gated calcium currents in gonadotropin-releasing hormone (GnRH) neurons.

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Sun, Jianli; Moenter, Suzanne M

2010-11-01

GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (I(Ca)) was recorded in the morning or afternoon 8-12 d after surgery using whole-cell voltage-clamp. I(Ca) was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. I(Ca) in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type-mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function.

GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.

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Naugle, Michelle M; Gore, Andrea C

2014-01-01

Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.

MR imaging of pulsatile CSF movement in hydrocephalus communicans before and after CSF shunt implantation

International Nuclear Information System (INIS)

Goldmann, A.; Kunz, U.; Rotermund, F.; Friedrich, J.M.; Schnarkowski, P.

1992-01-01

16 patients with hydrocephalus communicans and 5 healthy volunteers were examined to demonstrate the pattern of the pulsatile CSF flow. After implantation of a CSF shunt system the same patients were examined again to show the influence of the shunt on the CSF pulsations. We used a flow-sensitised, cardiac-gated 2D FLASH sequence and analysed the phase and magnitude images. It could be shown that most patients (n=12) had a hyerdynamic pulsatile flow preoperatively. After shunt implantation the pulsatile CSF motion and the clinical symptoms were improved in 8 of these patients. MRI of pulsatile CSF flow movement seems to be a helpful noninvasive tool to estimate the prognosis of a shunt implantation in patients with hydrocephalus communicans. (orig.) [de

GnRH and prostaglandin-based synchronization protocols as alternatives to progestogen-based treatments in sheep.

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Rekik, M; Haile, A; Abebe, A; Muluneh, D; Goshme, S; Ben Salem, I; Hilali, M El-Dine; Lassoued, N; Chanyalew, Y; Rischkowsky, B

2016-12-01

The study investigated, for cycling sheep, synchronizing protocols simultaneously to the standard "P" protocol using progestogens priming with intravaginal devices and gonadotropin. In November 2014, 90 adult Menz ewes were assigned to either the "P" protocol, "PGF" treatment where oestrus and ovulation were synchronized using two injections of prostaglandin 11 days apart or a "GnRH" treatment where the ewes had their oestrus and ovulation synchronized with GnRH (day 0)-prostaglandin (day 6)-GnRH (day 9) sequence. The ewes were naturally mated at the induced oestrus and the following 36 days. Plasma progesterone revealed that 92% of the ewes were ovulating before synchronization and all, except one, ovulated in response to the applied treatments. All "P" ewes exhibited oestrus during the 96-hr period after the end of the treatments in comparison with only 79.3% and 73.3% for "PGF" and "GnRH" ewes, respectively (p sheep after the rainy season when most animals are spontaneously cycling. © 2016 Blackwell Verlag GmbH.

Non-dimensional physics of pulsatile cardiovascular networks and energy efficiency.

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Yigit, Berk; Pekkan, Kerem

2016-01-01

In Nature, there exist a variety of cardiovascular circulation networks in which the energetic ventricular load has both steady and pulsatile components. Steady load is related to the mean cardiac output (CO) and the haemodynamic resistance of the peripheral vascular system. On the other hand, the pulsatile load is determined by the simultaneous pressure and flow waveforms at the ventricular outlet, which in turn are governed through arterial wave dynamics (transmission) and pulse decay characteristics (windkessel effect). Both the steady and pulsatile contributions of the haemodynamic power load are critical for characterizing/comparing disease states and for predicting the performance of cardiovascular devices. However, haemodynamic performance parameters vary significantly from subject to subject because of body size, heart rate and subject-specific CO. Therefore, a 'normalized' energy dissipation index, as a function of the 'non-dimensional' physical parameters that govern the circulation networks, is needed for comparative/integrative biological studies and clinical decision-making. In this paper, a complete network-independent non-dimensional formulation that incorporates pulsatile flow regimes is developed. Mechanical design variables of cardiovascular flow systems are identified and the Buckingham Pi theorem is formally applied to obtain the corresponding non-dimensional scaling parameter sets. Two scaling approaches are considered to address both the lumped parameter networks and the distributed circulation components. The validity of these non-dimensional number sets is tested extensively through the existing empirical allometric scaling laws of circulation systems. Additional validation studies are performed using a parametric numerical arterial model that represents the transmission and windkessel characteristics, which are adjusted to represent different body sizes and non-dimensional haemodynamic states. Simulations demonstrate that the proposed non

The effect of intracerebroventricular injection of L-glutamate on the hypothalamic GnRH content in rat

International Nuclear Information System (INIS)

Fu Qiang; He Haoming

2001-01-01

Objective: To investigate the effect of intracerebroventricular injection of L-Glutamate (L-Glu) on hypothalamic gonadotrophin-releasing hormone (GnRH) content in male rats. Methods: The GnRH content in the supernatant of hypothalamic homogenates was measured by RIA. Results: The mean values of hypothalamic GnRH content in rat were 1.59 +- 0.41, 0.88 +- 0.34, 0.70 +- 0.42 ng/10mg wet tissue 40 min after intracerebroventricular injection of 0.01176, 0.1176, 1.176 μg/20 μl L-Glu respectively, which were significantly lower than those in controls with saline injections (P 3 H-Glu in rat at 40 min the author found that the intake of 3 H-glu by MBH was 1069.82 +- 490.33 cpm/10 mg wet tissues, the highest value among those taken by cerebrum, cerebellum, pituitary, POA and MBH itself. Conclusion: L-Glu probably participates in the regulation of functional activity of GnRH neurons in the hypothalamus

Development of a gastroretentive pulsatile drug delivery platform.

Science.gov (United States)

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

DEFF Research Database (Denmark)

Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

2007-01-01

and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

Science.gov (United States)

Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Increasing awareness with recognition of pulsatile tinnitus for nurse practitioners in the primary care setting: A case study.

Science.gov (United States)

Vecchiarelli, Kelly; Amar, Arun Paul; Emanuele, Donna

2017-09-01

Pulsatile tinnitus is a whooshing sound heard synchronous with the heartbeat. It is an uncommon symptom affecting fewer than 10% of patients with tinnitus. It often goes unrecognized in the primary care setting. Failure to recognize this symptom can result in a missed or delayed diagnosis of a potentially life-threatening condition known as a dural arteriovenous fistula. The purpose of this case study is to provide a structured approach to the identification of pulsatile tinnitus and provide management recommendations. A case study and review of pertinent literature. Pulsatile tinnitus usually has a vascular treatable cause. A comprehensive history and physical examination will alert the nurse practitioner (NP) when pulsatile tinnitus is present. Auscultation in specific areas of the head can detect audible or objective pulsatile tinnitus. Pulsatile tinnitus that is audible to the examiner is an urgent medical condition requiring immediate consultation and referral. Knowledge of pulsatile tinnitus and awareness of this often treatable condition directs the NP to perform a detailed assessment when patients present with tinnitus, directs appropriate referral for care and treatment, and can reduce the risk of delayed or missed diagnosis. ©2017 American Association of Nurse Practitioners.

Superior vena cava syndrome after pulsatile bidirectional Glenn shunt procedure: Perioperative implications

Directory of Open Access Journals (Sweden)

Neema Praveen

2009-01-01

Full Text Available Bidirectional superior cavopulmonary shunt (bidirectional Glenn shunt is generally performed in many congenital cardiac anomalies where complete two ventricle circulations cannot be easily achieved. The advantages of BDG shunt are achieved by partially separating the pulmonary and systemic venous circuits, and include reduced ventricular preload and long-term preservation of myocardium. The benefits of additional pulsatile pulmonary blood flow include the potential growth of pulmonary arteries, possible improvement in arterial oxygen saturation, and possible prevention of development of pulmonary arteriovenous malformations. However, increase in the systemic venous pressure after BDG with additional pulsatile blood flow is known. We describe the peri-operative implications of severe flow reversal in the superior vena cava after pulsatile BDG shunt construction in a child who presented for surgical interruption of the main pulmonary artery.

Neuropeptides linking the control of appetite with reproductive function in domestic animals

Science.gov (United States)

The occurrence of puberty and maintenance of normal reproductive cycles are regulated by secretion of gonadotropin hormones from the pituitary gland, which is dependent upon the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. It is well established that secretion of...

Uric acid association with pulsatile and steady components of central and peripheral blood pressures.

Science.gov (United States)

Lepeytre, Fanny; Lavoie, Pierre-Luc; Troyanov, Stéphan; Madore, François; Agharazii, Mohsen; Goupil, Rémi

2018-03-01

Whether the cardiovascular risk attributed to elevated uric acid levels may be explained by changes in central and peripheral pulsatile and/or steady blood pressure (BP) components remains controversial. In a cross-sectional analysis of normotensive and untreated hypertensive participants of the CARTaGENE populational cohort, we examined the relationship between uric acid, and both pulsatile and steady components of peripheral and central BP, using sex-stratified linear regressions. Of the 20 004 participants, 10 161 individuals without antihypertensive or uric acid-lowering drugs had valid pulse wave analysis and serum uric acid levels. In multivariate analysis, pulsatile components of BP were not associated with uric acid levels, whereas steady components [mean BP (MBP), peripheral and central DBP] were all associated with higher levels of uric acid levels in women and men (all P uric acid levels but not for MBP-adjusted cSBP. Peripheral and cSBP, which are aggregate measures of pulsatile and steady BP, were also associated with uric acid levels in women (β = 0.063 and 0.072, respectively, both P uric acid levels. Serum uric acid levels appear to be associated with both central and peripheral steady but not pulsatile BP, regardless of sex.

Identification and characterization of a reptilian GnRH receptor from the leopard gecko.

Science.gov (United States)

Ikemoto, T; Enomoto, M; Park, M K

2004-02-12

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the regulation of reproductive functions through interactions with its specific receptor. We describe the first molecular cloning and characterization of a full-length GnRH receptor (GnRHR) from the leopard gecko Eublepharis macularius. It has a distinct genomic structure consisting of five exons and four introns, compared with all the other reported GnRHR genes. A native GnRH form, cGnRH-II, stimulated inositol phosphate (IP) production in COS-7 cells transiently transfected with the GnRHR, in a dose dependent manner. The mRNA was expressed in all the tissues and organs examined. Molecular phylogenetic analysis revealed that the cloned GnRHR belongs to the type 2/nonmammalian I GnRHR. Low-expression levels were observed from the pituitary glands of reproductively active leopard geckos, indicating the possibility that there is at least one more type of GnRHR highly expressed in the pituitary gland for the gonadotropin secretion in this reptile.

Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

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Tomoko eSoga

2016-03-01

Full Text Available Kisspeptin, a newly discovered neuropeptide regulates gonadotropin-releasing hormone (GnRH. Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by kiss1 gene is a 145-amino acid- protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein coupled receptor 54 (GPR54 has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP labelled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP–GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1nM treatment for 36h on GnRH migration. Furthermore to determine kisspeptin-induced molecular pathways related with apoptosis, and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser captured EGFP–GnRH neurons by real time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd 26 in EGFP–GnRH neurons was up-regulated by the exposure to kisspeptin. These studies suggest that ankrd26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.

GnRH Neurons on LSD: A Year of Rejecting Hypotheses That May Have Made Karl Popper Proud.

Science.gov (United States)

Moenter, Suzanne M

2018-01-01

Gonadotropin-releasing hormone (GnRH) neurons are critical to many aspects of fertility regulation, from producing episodic release critical to both sexes, to providing a central signal to induce the ovulatory cascade in females. This year saw progress through the rejection, and occasional support, of hypotheses in understanding how GnRH neurons contribute to these processes. This brief review provides one laboratory's view of new insights into possible roles for these cells in development, adult reproductive function, and what may go wrong with GnRH neurons in some cases of infertility. Copyright © 2018 Endocrine Society.

The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics

DEFF Research Database (Denmark)

Muñoz, Manuel; Cruz, María; Humaidan, Peter

2013-01-01

in the Instituto Valenciano de Infertilidad (IVI) Alicante and the Instituto Universitario-IVI Valencia, Spain, 2817 embryos deriving from 400 couples undergoing oocyte donation were analysed. After controlled ovarian stimulation and IVF/intracytoplamic sperm injection, the timing of embryonic cleavages......OBJECTIVE: To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist+hCG triggering versus GnRH antagonist+GnRH agonist triggering) affect embryo development and kinetics. STUDY DESIGN: In a retrospective cohort study...... was assessed by a video time-lapse system. The results were analysed using Student's t test for comparison of timings (hours) and Chi-squared test for comparison of proportions. A p-value...

Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

Directory of Open Access Journals (Sweden)

Imre Farkas

Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

Pulsatility role in cylinder flow dynamics at low Reynolds number

KAUST Repository

Qamar, Adnan

2012-01-01

We present dynamics of pulsatile flow past a stationary cylinder characterized by three non-dimensional parameters: the Reynolds number (Re), non-dimensional amplitude (A) of the pulsatile flow velocity, and Keulegan-Carpenter number (KC = Uo/Dωc). This work is motivated by the development of total artificial lungs (TAL) device, which is envisioned to provide ambulatory support to patients. Results are presented for 0.2 ≤ A ≤ 0.6 and 0.57 ≤ KC ≤ 2 at Re = 5 and 10, which correspond to the operating range of TAL. Two distinct fluid regimes are identified. In both regimes, the size of the separated zone is much greater than the uniform flow case, the onset of separation is function of KC, and the separation vortex collapses rapidly during the last fraction of the pulsatile cycle. The vortex size is independent of KC, but with an exponential dependency on A. In regime I, the separation point remains attached to the cylinder surface. In regime II, the separation point migrates upstream of the cylinder. Two distinct vortex collapse mechanisms are observed. For A < 0.4 and all KC and Re values, collapse occurs on the cylinder surface, whereas for A > 0.4 the separation vortex detaches from the cylinder surface and collapses at a certain distance downstream of the cylinder. The average drag coefficient is found to be independent of A and KC, and depends only on Re. However, for A > 0.4, for a fraction of the pulsatile cycle, the instantaneous drag coefficient is negative indicating a thrust production. © 2012 American Institute of Physics.

Differential roles of PKC isoforms (PKCs) in GnRH stimulation of MAPK phosphorylation in gonadotrope derived cells.

Science.gov (United States)

Mugami, Shany; Dobkin-Bekman, Masha; Rahamim-Ben Navi, Liat; Naor, Zvi

2018-03-05

The role of protein kinase C (PKC) isoforms (PKCs) in GnRH-stimulated MAPK [ERK1/2, JNK1/2 and p38) phosphorylation was examined in gonadotrope derived cells. GnRH induced a protracted activation of ERK1/2 and a slower and more transient activation of JNK1/2 and p38MAPK. Gonadotropes express conventional PKCα and PKCβII, novel PKCδ, PKCε and PKCθ, and atypical PKC-ι/λ. The use of green fluorescent protein (GFP)-PKCs constructs revealed that GnRH induced rapid translocation of PKCα and PKCβII to the plasma membrane, followed by their redistribution to the cytosol. PKCδ and PKCε localized to the cytoplasm and Golgi, followed by the rapid redistribution by GnRH of PKCδ to the perinuclear zone and of PKCε to the plasma membrane. The use of dominant negatives for PKCs and peptide inhibitors for the receptors for activated C kinase (RACKs) has revealed differential role for PKCα, PKCβII, PKCδ and PKCε in ERK1/2, JNK1/2 and p38MAPK phosphorylation in a ligand-and cell context-dependent manner. The paradoxical findings that PKCs activated by GnRH and PMA play a differential role in MAPKs phosphorylation may be explained by persistent vs. transient redistribution of selected PKCs or redistribution of a given PKC to the perinuclear zone vs. the plasma membrane. Thus, we have identified the PKCs involved in GnRH stimulated MAPKs phosphorylation in gonadotrope derived cells. Once activated, the MAPKs will mediate the transcription of the gonadotropin subunits and GnRH receptor genes. Copyright © 2017. Published by Elsevier B.V.

Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles.

Science.gov (United States)

Park, Hanwook; Yeom, Eunseop; Seo, Seung-Jun; Lim, Jae-Hong; Lee, Sang-Joon

2015-03-06

Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases.

Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles

Science.gov (United States)

Park, Hanwook; Yeom, Eunseop; Seo, Seung-Jun; Lim, Jae-Hong; Lee, Sang-Joon

2015-01-01

Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases. PMID:25744850

Experimental Investigation of Pulsatile Flow in Circular Tubes

Czech Academy of Sciences Publication Activity Database

Adamec, J.; Nožička, J.; Hanus, D.; Kořenář, Josef

2001-01-01

Roč. 17, č. 5 (2001), s. 1133-1136 ISSN 0748-4658 Institutional research plan: CEZ:AV0Z2060917 Keywords : pulsatile flow * laminar-turbulent transition * reynolds normal stress Subject RIV: BK - Fluid Dynamics Impact factor: 0.418, year: 2001

Evaluation of hepatic venous pulsatility and portal venous velocity with doppler ultrasonography during the puerperium

Energy Technology Data Exchange (ETDEWEB)

Pekindil, Goekhan [Department of Radiology, Trakya University School of Medicine, 22030 Edirne (Turkey); Varol, Fuesun G. [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey); Ali Yuece, M. [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey); Yardim, Turgut [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey)

1999-03-01

Objective: The aim of this study is to evaluate pregnancy-induced changes of hepatic venous pulsatility and portal venous velocity in the puerperium and to determine if these changes disappeared by the end of the puerperium. Methods and material: Healthy normal volunteers (90) were examined on the 2nd and 7th days of puerperium and between the 6th and 8th weeks postpartum. Doppler waveform patterns were obtained in the middle hepatic vein and main portal vein. The hepatic venous pulsatility was named as normal, damped or flat. Results: On the 2nd day postpartum, the hepatic vein pulsatility was shown as normal in 8 (26%), damped in 11 (37%) and flat in 11 (37%) cases. On the 7th day postpartum, 15 (50%) cases had normal, 9 (30%) cases had dampened, and 6 (20%) cases had still flat pattern. The majority of the cases (60%) displayed normal hepatic venous pulsatility in the 6th and 8th weeks of puerperium, whereas 23% had still dampened and 17% had flat patterns. There was a trend toward normal pulsatility with increasing puerperal age. The mean portal venous velocity was still higher than the non-pregnant levels and did not showed significant alterations during puerperium. Conclusion: This study emphasised that, since pregnancy-induced alterations in hepatic venous pulsatility and portal venous velocity had not completely returned to normal in most cases until the end of the puerperium, these physiological changes should be considered whenever hepatic and portal systems are interpreted with Doppler sonography during the puerperal period.

Evaluation of hepatic venous pulsatility and portal venous velocity with doppler ultrasonography during the puerperium

International Nuclear Information System (INIS)

Pekindil, Goekhan; Varol, Fuesun G.; Ali Yuece, M.; Yardim, Turgut

1999-01-01

Objective: The aim of this study is to evaluate pregnancy-induced changes of hepatic venous pulsatility and portal venous velocity in the puerperium and to determine if these changes disappeared by the end of the puerperium. Methods and material: Healthy normal volunteers (90) were examined on the 2nd and 7th days of puerperium and between the 6th and 8th weeks postpartum. Doppler waveform patterns were obtained in the middle hepatic vein and main portal vein. The hepatic venous pulsatility was named as normal, damped or flat. Results: On the 2nd day postpartum, the hepatic vein pulsatility was shown as normal in 8 (26%), damped in 11 (37%) and flat in 11 (37%) cases. On the 7th day postpartum, 15 (50%) cases had normal, 9 (30%) cases had dampened, and 6 (20%) cases had still flat pattern. The majority of the cases (60%) displayed normal hepatic venous pulsatility in the 6th and 8th weeks of puerperium, whereas 23% had still dampened and 17% had flat patterns. There was a trend toward normal pulsatility with increasing puerperal age. The mean portal venous velocity was still higher than the non-pregnant levels and did not showed significant alterations during puerperium. Conclusion: This study emphasised that, since pregnancy-induced alterations in hepatic venous pulsatility and portal venous velocity had not completely returned to normal in most cases until the end of the puerperium, these physiological changes should be considered whenever hepatic and portal systems are interpreted with Doppler sonography during the puerperal period

Generation of tunable and pulsatile concentration gradients via microfluidic network

KAUST Repository

Zhou, Bingpu

2014-06-04

We demonstrate a compact Polydimethylsiloxane microfluidic chip which can quickly generate ten different chemical concentrations simultaneously. The concentration magnitude of each branch can be flexibly regulated based on the flow rate ratios of the two injecting streams. The temporal/pulsatile concentration gradients are achieved by integrating on-chip pneumatic actuated valves controlled by the external signals. The temporal concentration gradients can also be tuned precisely by varying applied frequency and duty cycle of the trigger signal. It is believed that such microdevice will be potentially used for some application areas of producing stable chemical gradients as well as allowing fast, pulsatile gradient transformation in seconds.

Developmental expression of the G protein-coupled receptor 54 and three GnRH mRNAs in the teleost fish cobia.

Science.gov (United States)

Mohamed, J Shaik; Benninghoff, Abby D; Holt, G Joan; Khan, Izhar A

2007-02-01

The cDNAs of the G protein-coupled receptor 54 (GPR54) and three prepro-gonadotropin-releasing hormones, GnRH-I (seabream GnRH), GnRH-II (chicken GnRH-II), and GnRH-III (salmon GnRH) were isolated and cloned from the brain of the teleost fish cobia, Rachycentron canadum. The cobia GPR54 cDNA was 95 and 51-56% identical to those of tilapia and mammalian models respectively. The GnRH cDNA sequences of cobia showed strong identities to those of tilapia, Atlantic croaker, red drum, and the seabass and seabream species. The real-time quantitative RT-PCR methods allowed detection of all three GnRH mRNAs on the first day after hatching (DAH). The GnRH-I mRNA levels, which were the lowest among the three GnRHs, increased gradually with two distinct peaks in larvae at 3 and 4 DAH. On the other hand, GnRH-II and GnRH-III mRNAs were significantly higher in larvae at 2 and 6 DAH compared with those on the preceding days. In addition, significant peaks of all the three GnRH mRNAs were observed in the brains of 26-day-old fish. The finding of higher GnRH-I and GnRH-II mRNAs in males than females at 153 DAH may be related to early puberty observed during the first year in laboratory-reared male cobia. Moreover, this study demonstrates for the first time the expression of GPR54 mRNA during larval development in a vertebrate species. The concomitant expression patterns of GPR54 and GnRH mRNAs during different stages of larval and juvenile developments, and during early puberty in male cobia suggest a potential relationship between GPR54 and multiple GnRHs during these stages of development consistent with the role of GPR54 in controlling GnRH release in mammals. The increase in GPR54 and GnRH mRNAs observed during early puberty in cobia is consistent with a similar change reported in pubertal rats. This finding together with the localization of GPR54 mRNAs on GnRH neurons in fish and mammals suggests that the GPR54-GnRH interactions may be conserved in different vertebrate groups.

Genetic variation in total number and locations of GnRH neurons identified using in situ hybridization in a wild-source population.

Science.gov (United States)

Kaugars, Katherine E; Rivers, Charlotte I; Saha, Margaret S; Heideman, Paul D

2016-02-01

The evolution of brain function in the regulation of physiology may depend in part upon the numbers and locations of neurons. Wild populations of rodents contain natural genetic variation in the inhibition of reproduction by winter-like short photoperiod, and it has been hypothesized that this functional variation might be due in part to heritable variation in the numbers or location of gonadotropin releasing hormone (GnRH) neurons. A naturally variable wild-source population of white-footed mice was used to develop lines artificially selected for or against mature gonads in short, winter-like photoperiods. We compared a selection line that is reproductively inhibited in short photoperiod (Responsive) to a line that is weakly inhibited by short photoperiod (Nonresponsive) for differences in counts of neurons identified using in situ hybridization for GnRH mRNA. There was no effect of photoperiod, but there were 60% more GnRH neurons in total in the Nonresponsive selection line than the Responsive selection line. The lines differed specifically in numbers of GnRH neurons in more anterior regions, whereas numbers of GnRH neurons in posterior areas were not statistically different between lines. We compare these results to those of an earlier study that used immunohistochemical labeling for GnRH neurons. The results are consistent with the hypothesis that the selection lines and natural source population contain significant genetic variation in the number and location of GnRH neurons. The variation in GnRH neurons may contribute to functional variation in fertility that occurs in short photoperiods in the laboratory and in the wild source population in winter. © 2015 Wiley Periodicals, Inc.

An in vitro experimental study of flow past aortic valve under varied pulsatile conditions

Science.gov (United States)

Zhang, Ruihang; Zhang, Yan

2017-11-01

Flow past aortic valve represents a complex fluid-structure interaction phenomenon that involves pulsatile, vortical, and turbulent conditions. The flow characteristics immediately downstream of the valve, such as the variation of pulsatile flow velocity, formation of vortices, distribution of shear stresses, are of particular interest to further elucidate the role of hemodynamics in various aortic diseases. However, the fluid dynamics of a realistic aortic valve is not fully understood. Particularly, it is unclear how the flow fields downstream of the aortic valve would change under varied pulsatile inlet boundary conditions. In this study, an in vitro experiment has been conducted to investigate the flow fields downstream of a silicone aortic valve model within a cardiovascular flow simulator. Phased-locked Particle Image Velocimetry measurements were performed to map the velocity fields and Reynolds normal and shear stresses at different phases in a cardiac cycle. Temporal variations of pressure across the valve model were measured using high frequency transducers. Results have been compared for different pulsatile inlet conditions, including varied frequencies (heart rates), magnitudes (stroke volumes), and cardiac contractile functions (shapes of waveforms).

Long-term effects of GnRH agonists on fertility and behaviour

DEFF Research Database (Denmark)

Goericke-Pesch, Sandra Kathrin

2017-01-01

; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option...... and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long......-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal....

Six-month gonadotropin releasing hormone (GnRH agonist depots provide efficacy, safety, convenience, and comfort

Directory of Open Access Journals (Sweden)

Phillips JM

2011-07-01

Full Text Available E David Crawford, Jason M PhillipsUniversity of Colorado Health Sciences Center, Aurora, CO, USAAbstract: Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelinpalmoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone #50 ng/dL that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.Keywords: prostate cancer, leuprorelin, leuprolide, triptorelin, 6-month depot, testosterone

Closing in on the Mechanisms of Pulsatile Insulin Secretion.

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Bertram, Richard; Satin, Leslie S; Sherman, Arthur S

2018-03-01

Insulin secretion from pancreatic islet β-cells occurs in a pulsatile fashion, with a typical period of ∼5 min. The basis of this pulsatility in mouse islets has been investigated for more than four decades, and the various theories have been described as either qualitative or mathematical models. In many cases the models differ in their mechanisms for rhythmogenesis, as well as other less important details. In this Perspective, we describe two main classes of models: those in which oscillations in the intracellular Ca 2+ concentration drive oscillations in metabolism, and those in which intrinsic metabolic oscillations drive oscillations in Ca 2+ concentration and electrical activity. We then discuss nine canonical experimental findings that provide key insights into the mechanism of islet oscillations and list the models that can account for each finding. Finally, we describe a new model that integrates features from multiple earlier models and is thus called the Integrated Oscillator Model. In this model, intracellular Ca 2+ acts on the glycolytic pathway in the generation of oscillations, and it is thus a hybrid of the two main classes of models. It alone among models proposed to date can explain all nine key experimental findings, and it serves as a good starting point for future studies of pulsatile insulin secretion from human islets. © 2018 by the American Diabetes Association.

Enhancement of Arterial Pressure Pulsatility by Controlling Continuous-Flow Left Ventricular Assist Device Flow Rate in Mock Circulatory System.

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Bozkurt, Selim; van de Vosse, Frans N; Rutten, Marcel C M

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase the arterial pulse pressure and pulsatility by controlling the CF-LVAD flow rate. A MicroMed DeBakey pump was used as the CF-LVAD. A model simulating the flow rate through the aortic valve was used as a reference model to drive the pump. A mock circulation containing two synchronized servomotor-operated piston pumps acting as left and right ventricles was used as a circulatory system. Proportional-integral control was used as the control method. First, the CF-LVAD was operated at a constant speed. With pulsatile-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. Continuous and pulsatile-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility increased significantly for both arterial pressure and pump flow rate signals under pulsatile speed pump support. This study shows the possibility of improving the pulsatility of CF-LVAD support by regulating pump speed over a cardiac cycle without reducing the overall level of support.

Positron emission particle tracking in pulsatile flow

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Patel, Nitant; Ruggles, Arthur [University of Tennessee-Knoxville, Department of Nuclear Engineering, Knoxville, TN (United States); Wiggins, Cody [University of Tennessee-Knoxville, Department of Physics and Astronomy, Knoxville, TN (United States)

2017-05-15

Positron emission particle tracking (PEPT) is increasingly used to understand the flow characteristics in complex systems. This research utilizes PEPT to measure pulsatile flow of frequency 2.1 Hz in an elastic Masterkleer PVC tube of 19 mm inner diameter and 3.2 mm wall thickness. Anion exchange resin beads are labeled with {sup 18}F and delivered to a pump driven flow loop with motorized ball valve used to develop the pulsatile flow. Data are collected in the tube with circular cross section, and measurements are also collected with a section of the tube pinched. Nominal flow velocities are near 1 m/s and Reynolds numbers near 20,000. Many thousand PEPT particle traces are collected and synchronized with the flow pulsation. These Lagrangian data are presented as a series of 20 still frames depicting the 3-D velocity field present during each phase of the flow pulsation. Pressure data are also collected to resolve the pressure wave front moving through the open elastic tube at velocity 15.2 m/s. (orig.)

Pulsatile flow in ventricular catheters for hydrocephalus

Science.gov (United States)

Giménez, Á.; Galarza, M.; Thomale, U.; Schuhmann, M. U.; Valero, J.; Amigó, J. M.

2017-05-01

The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

GnRH signalling pathways and GnRH-induced homologous desensitization in a gonadotrope cell line (alphaT3-1).

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Poulin, B; Rich, N; Mas, J L; Kordon, C; Enjalbert, A; Drouva, S V

1998-07-25

Exposure of the gonadotrope cells to gonadotropin-releasing hormone (GnRH) reduces their responsiveness to a new GnRH stimulation (homologous desensitization). The time frame as well as the mechanisms underlying this phenomenon are yet unclear. We studied in a gonadotrope cell line (alphaT3-1) the effects of short as well as long term GnRH pretreatments on the GnRH-induced phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities, by measuring the production of IP3, total inositol phosphates (IPs), arachidonic acid (AA) and phosphatidylethanol (PEt) respectively. We demonstrated that although rapid desensitization of GnRH-induced IP3 formation did not occur in these cells, persistent stimulation of cells with GnRH or its analogue resulted in a time-dependent attenuation of GnRH-elicited IPs formation. GnRH-induced IPs desensitization was potentiated after direct activation of PKC by the phorbol ester TPA, suggesting the involvement of distinct mechanisms in the uncoupling exerted by either GnRH or TPA on GnRH-stimulated PI hydrolysis. The levels of individual phosphoinositides remained unchanged under any desensitization condition applied. Interestingly, while the GnRH-induced PLA2 activity was rapidly desensitized (2.5 min) after GnRH pretreatments, the neuropeptide-evoked PLD activation was affected at later times, indicating an important time-dependent contribution of these enzymatic activities in the sequential events underlying the GnRH-induced homologous desensitization processes in the gonadotropes. Under GnRH desensitization conditions, TPA was still able to induce PLD activation and to further potentiate the GnRH-evoked PLD activity. AlphaT3-1 cells possess several PKC isoforms which, except PKCzeta, were differentially down-regulated by TPA (PKCalpha, betaII, delta, epsilon, eta) or GnRH (PKCbetaII, delta, epsilon, eta). In spite of the presence of PKC inhibitors or down-regulation of PKC isoforms by TPA, the desensitizing effect of the neuropeptide on

Fertility of Angus cross beef heifers after GnRH treatment on day 23 and timing of insemination in 14-day CIDR protocol.

Science.gov (United States)

Kasimanickam, R K; Hall, J B; Whittier, W D

2017-02-01

This study compared artificial insemination pregnancy rate (AI-PR) between 14-day CIDR-GnRH-PGF2α-GnRH and CIDR-PGF2α-GnRH synchronization protocol with two fixed AI times (56 or 72 hr after PGF2α). On day 0, heifers (n = 1311) from nine locations assigned body condition score (BCS: 1, emaciated; 9, obese), reproductive tract score (RTS: 1, immature, acyclic; 5, mature, cyclic) and temperament score (0, calm; and 1, excited) and fitted with a controlled internal drug release (CIDR, 1.38 g of progesterone) insert for 14 days. Within herd, heifers were randomly assigned either to no-GnRH group (n = 635) or to GnRH group (n = 676), and heifers in GnRH group received 100 μg of GnRH (gonadorelin hydrochloride, IM) on day 23. All heifers received 25 mg of PGF2α (dinoprost, IM) on day 30 and oestrous detection aids at the same time. Heifers were observed for oestrus thrice daily until AI. Within GnRH groups, heifers were randomly assigned to either AI-56 or AI-72 groups. Heifers in AI-56 group (n = 667) were inseminated at 56 hr (day 32 PM), and heifers in AI-72 group (n = 644) were inseminated at 72 hr (day 33 AM) after PGF2α administration. All heifers were given 100 μg of GnRH concurrently at the time AI. Controlling for BCS (p < .05), RTS (p < .05), oestrous expression (p < .001), temperament (p < .001) and GnRH treatment by time of insemination (p < .001), the AI-PR differed between GnRH treatment [GnRH (Yes - 60.9% (412/676) vs. No - 55.1% (350/635); p < .05)] and insemination time [AI-56 - 54.6% (364/667) vs. AI-72 - 61.8% (398/644); (p < .01)] groups. The GnRH treatment by AI time interaction influenced AI-PR (GnRH56 - 61.0% (208/341); GnRH72 - 60.9% (204/335); No-GnRH56 - 47.9% (156/326); No-GnRH72 - 62.8% (194/309); p < .001). In conclusion, 14-day CIDR synchronization protocol for FTAI required inclusion of GnRH on day 23 if inseminations were to be performed at 56 hr after PGF2α in order to achieve greater AI-PR. �

Is the use of low-pressure pulsatile lavage for pressure ulcer management associated with environmental contamination with Acinetobacter baumannii?

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Ho, Chester H; Johnson, Tova; Miklacic, Joan; Donskey, Curtis J

2009-10-01

Ho CH, Johnson T, Miklacic J, Donskey CJ. Is the use of low-pressure pulsatile lavage for pressure ulcer management associated with environmental contamination with Acinetobacter baumannii? To determine the extent of environmental contamination associated with low-pressure pulsatile lavage of stage III or IV pressure ulcers in patients with spinal cord injury (SCI) when routine infection control precautions are used for wounds colonized or infected with Acinetobacter baumannii. Prospective investigation in which pressure ulcer cultures and environmental cultures were obtained before and after low-pressure pulsatile lavage treatment, and before and after regular dressing changes. Environmental cultures included the patient's bedrail and settle plates placed 0.6, 1.5, and 2.4m from the wound to assess airborne spread of A. baumannii. SCI inpatient unit in a Department of Veterans Affairs Medical Center. Inpatients (N=15) with SCI receiving daily low-pressure pulsatile lavage treatment for stage III or IV pressure ulcers with standard dressing change, as well as regular dressing changes without low-pressure pulsatile lavage at other times of the day. Standard, regular dressing changes and dressing changes with low-pressure pulsatile lavage. Comparison of frequency of environmental contamination with A. baumannii associated with low-pressure pulsatile lavage versus regular dressing changes. Of the 15 SCI inpatients meeting inclusion criteria, 9 (60%) grew A. baumannii from their wounds. Of the 9 patients with wound cultures positive for A. baumannii, only 1 (11%) had environmental contamination with this organism after performance of low-pressure pulsatile lavage, and the same patient had environmental contamination after a standard dressing change. The antibiotic susceptibility patterns of the wound and environmental A. baumannii isolates were identical. Low-pressure pulsatile lavage using the infection control methods described is not associated with an increased

Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension?

Science.gov (United States)

Lansley, J A; Tucker, W; Eriksen, M R; Riordan-Eva, P; Connor, S E J

2017-09-01

Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus ( n = 42), without pulsatile tinnitus ( n = 37), and controls ( n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls ( P tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls ( P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum

Pulsatile blood flow, shear force, energy dissipation and Murray's Law

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Bengtsson Hans-Uno

2006-08-01

Full Text Available Abstract Background Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. Methods To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. Results For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches of the arterial system. Conclusion A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

Imaging findings of pulsatile tinnitus caused by sigmoid sinus abnormalities

International Nuclear Information System (INIS)

Liang Xihong; Wang Zhenchang; Gong Shusheng; Xia Yin; Wang Zhengyu; Yang Bentao; Yan Fei; Li Jing; Xian Junfang; Chen Guangli

2010-01-01

Objective: To study a rare CT finding of pulsatile tinnitus (PT) caused by sigmoid sinus abnormalities. Methods: The imaging data of PT caused by sigmoid sinus abnormalities were analyzed retrospectively in 15 patients (15 female). The median age was 45 years (24 to 63 years). The duration of persistence pulsatile tinnitus was from 0.5 year to 36.0 years (median time, 2.0 years). The tinnitus was at left side in 5 patients and right side in 10 patients. Fifteen patients underwent HRCT of the temporal bone. Of them, 12 patients underwent cerebral CT angiography and CT venogram (CTA/CTV), and 9 patients underwent cerebral digital subtraction angiography (DSA). Nine patients underwent transmastoid reconstruction surgery of the sigmoid sinus. Of them, the tinnitus was at left side in 2 patients and right side in 7 patients. Paired rank sum test was used to compare the cross-sectional area of the sigmoid sinus of the tinnitus side and normal side.Results: On HRCT, foca bony coarse defect is shown in the anterior sigmoid wall in 11 patients and anterolateral sigmoid wall in 4 patients. On CTA/CTV, the sigmoid sinus focally protuded into the adjacent mastoid air cells and formed diverticulum in 10 patients. The pulsatile tinnitus disappeared immediately after transmastoid reconstruction surgery of the sigmoid sinus in all 9 patients. The cross-sectional area of the sigmoid sinus of the tinnitus side was 100.6 (41.5-96.2)mm 2 , it was 77.0 (92.1-122.4)mm 2 in the nonmal side (Z=2.158, P=0.031). Conclusion: Focal bony defect of the sigmoid wall with sigmoid sinus diverticula is one of the causes which lead to pulsatile tinnitus, which can be easily identified by imaging examination. (authors)

Imaging findings of pulsatile tinnitus caused by sigmoid sinus abnormalities

Energy Technology Data Exchange (ETDEWEB)

Xihong, Liang; Zhenchang, Wang; Shusheng, Gong; Yin, Xia; Zhengyu, Wang; Bentao, Yang; Fei, Yan; Jing, Li; Junfang, Xian; Guangli, Chen [Department of Radiology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing (China)

2010-04-15

Objective: To study a rare CT finding of pulsatile tinnitus (PT) caused by sigmoid sinus abnormalities. Methods: The imaging data of PT caused by sigmoid sinus abnormalities were analyzed retrospectively in 15 patients (15 female). The median age was 45 years (24 to 63 years). The duration of persistence pulsatile tinnitus was from 0.5 year to 36.0 years (median time, 2.0 years). The tinnitus was at left side in 5 patients and right side in 10 patients. Fifteen patients underwent HRCT of the temporal bone. Of them, 12 patients underwent cerebral CT angiography and CT venogram (CTA/CTV), and 9 patients underwent cerebral digital subtraction angiography (DSA). Nine patients underwent transmastoid reconstruction surgery of the sigmoid sinus. Of them, the tinnitus was at left side in 2 patients and right side in 7 patients. Paired rank sum test was used to compare the cross-sectional area of the sigmoid sinus of the tinnitus side and normal side.Results: On HRCT, foca bony coarse defect is shown in the anterior sigmoid wall in 11 patients and anterolateral sigmoid wall in 4 patients. On CTA/CTV, the sigmoid sinus focally protuded into the adjacent mastoid air cells and formed diverticulum in 10 patients. The pulsatile tinnitus disappeared immediately after transmastoid reconstruction surgery of the sigmoid sinus in all 9 patients. The cross-sectional area of the sigmoid sinus of the tinnitus side was 100.6 (41.5-96.2)mm{sup 2}, it was 77.0 (92.1-122.4)mm{sup 2} in the nonmal side (Z=2.158, P=0.031). Conclusion: Focal bony defect of the sigmoid wall with sigmoid sinus diverticula is one of the causes which lead to pulsatile tinnitus, which can be easily identified by imaging examination. (authors)

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

Science.gov (United States)

Moeller, John F; Meredith, Michael

2010-12-17

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of reproductive methods and GnRH administration on long-term protocol in Santa Ines ewes.

Science.gov (United States)

Biehl, Marcos V; Ferraz Junior, Marcos V C; Ferreira, Evandro M; Polizel, Daniel M; Miszura, Alexandre A; Barroso, José P R; Oliveira, Gabriela B; Bertoloni, Analisa V; Pires, Alexandre V

2017-08-01

This study aimed to determine whether reproductive performance of ewes submitted to laparoscopic timed artificial insemination (TAI) would be similar to ante meridiem (AM)/post meridiem (PM) rule and assisted natural mating (NM), and whether GnRH may enhance the pregnancy rate in TAI. In experiment I, 191 non-lactating ewes were synchronized, then TAI was performed either 48 h after progesterone (P4) removal (TAI-48 h) or 12 h after estrus detection (AM/PM); moreover, some ewes were submitted to NM (NM) as control treatment. In experiment II, 247 non-lactating ewes were allocated in five treatments, a control (no-GnRH on protocol) and four treatments arranged in a factorial design 2 × 2. The factors were time and dose of GnRH: ewes that received either 10 μg (TAI-10 μg-36 h) or 25 μg of GnRH (TAI-25 μg-36 h) 36 h after P4 removal and ewes that received either 10 μg (TAI-10 μg-48 h) or 25 μg of GnRH (TAI-25 μg-48 h) at time of insemination, 48 h after P4 removal. In experiment I, pregnancy rate in TAI-48 h was lower (P = 0.03) than AM/PM and NM. Moreover, the probability of pregnancy in TAI-48 h was higher (P = 0.06) in ewes detected in estrus early. In experiment II, the use of GnRH in TAI protocols increased (P < 0.01) pregnancy rate at synchronization, and TAI-25 μ-48 h and TAI-10 μg-36 h treatments increased (P = 0.02) pregnancy rate compered to TAI-10 μg-48 h. We conclude that TAI decreased pregnancy rate compered to NM and AM/PM, which may be improved by GnRH use in TAI to synchronize ovulation.

Effect of endotoxin on the expression of GnRH and GnRHR genes in the hypothalamus and anterior pituitary gland of anestrous ewes.

Science.gov (United States)

Herman, Andrzej Przemysław; Tomaszewska-Zaremba, Dorota

2010-07-01

An immune/inflammatory challenge can affect reproduction at the level of the hypothalamus, pituitary gland, or gonads. Nonetheless, the major impact is thought to occur within the brain or the pituitary gland. The present study was designed to examine the effect of intravenous (i.v.) lipopolysaccharide (LPS) injection on the expression of gonadotropin-releasing hormone (GnRH) and the gonadotropin-releasing hormone receptor (GnRHR) genes in the hypothalamic structures where GnRH neurons are located as well as in the anterior pituitary gland (AP) of anestrous ewes. We also determined the effect of LPS on luteinizing hormone (LH) release. It was found that i.v. LPS injection significantly decreased GnRH and GnRHR mRNAs levels in the preoptic area (40%, ppituitary cells to GnRH stimulation. The presence of GnRH mRNA in the median eminence, the hypothalamic structure where GnRH-ergic neurons' terminals are located, suggests that the axonal transport of GnRH mRNA may occur in these neurons. This phenomenon could play an important role in the physiology of GnRH neurons. Our data demonstrate that immune stress could be important inhibitor of this process. Copyright 2010 Elsevier B.V. All rights reserved.

The Characteristics of Turbulence in Curved Pipes under Highly Pulsatile Flow Conditions

Science.gov (United States)

Kalpakli, A.; Örlü, R.; Tillmark, N.; Alfredsson, P. Henrik

High speed stereoscopic particle image velocimetry has been employed to provide unique data from a steady and highly pulsatile turbulent flow at the exit of a 90 degree pipe bend. Both the unsteady behaviour of the Dean cells under steady conditions, the so called "swirl switching" phenomenon, as well as the secondary flow under pulsations have been reconstructed through proper orthogonal decomposition. The present data set constitutes - to the authors' knowledge - the first detailed investigation of a turbulent, pulsatile flow through a pipe bend.

Pulsatile thyrotropin secretion in patients with Cushing's syndrome

NARCIS (Netherlands)

Adriaanse, R.; Brabant, G.; Endert, E.; Wiersinga, W. M.

1994-01-01

Pulsatile and circadian thyrotropin (TSH) secretion were studied in 16 healthy controls and in three patients with Cushing's syndrome who were studied twice (before and after treatment). Blood was sampled every 10 minutes over 24 hours for TSH (immunoradiometric assay [IRMA]). Mean 24-hour TSH in

Effects of GnRH administration on ovulation and fertility in ewes subjected to estrous synchronization

Directory of Open Access Journals (Sweden)

Amanda dos Santos Cavalcanti

2012-06-01

Full Text Available The objective of this study was to verify the effects of GnRH on ovulation and pregnancy of ewes subjected to a short-term synchronization of estrus. Santa Inês and crossbred Santa Inês/Dorper ewes received 60 mg MAP sponges during 6 days plus 300 IU eCG and 30 µg d-cloprostenol 24 h prior to sponge withdrawal (SW. Ewes were assigned to receive 0.9% NaCl solution (Tcontrol; n = 32 or 25 µg GnRH (licerelin, T GnRH; n = 34 24 hours after SW. Each group was assigned to intrauterine insemination by laparoscopy (n = 25 or to natural mating (n = 41. Artificial insemination was performed with a single dose of fresh semen. For controlled mating, females were exposed to males 12, 24, 36 and 48 hours after SW. Ten females per treatment were subjected to transrectal ultrasound examination at 12-hour intervals (SW to 60 hours after. Estrous response (100.0% vs 95.2%, interval from SW to estrus (32.9±7.4 vs 29.8±6.9 hours, estrous length (37.4±9.0 vs 31.5±10.4 hours, pregnancy rates (57.0% vs 41.0%, ovulation rate (100.0% vs 90.0%, number of ovulations/ewe (1.1±0.3 vs 1.2±0.4, maximum follicular diameter (6.4±0.7 vs 6.1±0.6 mm, interval from SW to ovulation (59.1±3.5 vs 58.4±3.5 hours did not differ between Tcontrol and T GnRH, respectively. Administration of GnRH 24 hours after SW does not improve ovulation or pregnancy rate in estrous synchronization in ewes.

Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

Science.gov (United States)

Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

2012-01-01

Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

Effects of GnRH, a progesterone-releasing device, and energy balance on an oestrus synchronisation program in anoestrous dairy cows.

Science.gov (United States)

Sahu, S K; Cockrem, J F; Parkinson, T J; Laven, R A

2017-08-01

The aim of this research was to study the roles of the day 0 energy balance and gonadotrophin-releasing hormone (GnRH) and progesterone levels on dominant follicle (DF) and corpus luteum (CL) development during the first 7 days of a gonadotrophin-prostaglandin-gonadotrophin (GPG) + progesterone (P4) program in anoestrous dairy cows. Cows (n = 81) were allocated to one of the three treatments: (1) GPG + P4 (days 0 and 9, 100 µg GnRH; day 0-7, intravaginal P4 device; day 7, 500 µg PGF 2α ); (2) GPG (as for treatment 1 but excluding the P4 device) and (3) prostaglandin + GnRH + P4 (as for treatment 1, but excluding day 0 GnRH). DF and CL size, plasma concentrations of insulin, insulin-like growth factor-I (IGF-I) and non-esterified fatty acid (NEFA) were measured on days 0 and 7. The proportion of cows with a CL on day 7 was significantly different between groups (GPG: 78%, GPG+P4: 69%, PGF 2α + GnRH + P4: 42%, P = 0.02). The CL volume on day 7 was significantly associated with treatment, treatment by time postpartum and plasma concentrations of insulin, IGF-I and NEFA. In cows without a CL present on day 0 of an oestrus synchronisation program, removal of the day 0 GnRH treatment led to reduced CL development; however, no effect of adding progesterone was found. In contrast, in cows with a CL present on day 0 inclusion of a progesterone device led to a higher CL volume, but removal of the first GnRH injection had no effect. Response to the treatment was affected by plasma concentrations of insulin, IGF-I and NEFA. © 2017 Australian Veterinary Association.

Pulsatile Lavage of Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification in a Rat Model.

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Chiaramonti, Alexander M; Robertson, Astor D; Nguyen, Thao P; Jaffe, David E; Hanna, E Lex; Holmes, Robert; Barfield, William R; Fourney, William L; Stains, Joseph P; Pellegrini, Vincent D

2017-11-01

Adequate irrigation of open musculoskeletal injuries is considered the standard of care to decrease bacterial load and other contaminants. While the benefit of debris removal compared with the risk of further seeding by high-pressure lavage has been studied, the effects of irrigation on muscle have been infrequently reported. Our aim in the present study was to assess relative damage to muscle by pulsatile lavage compared with bulb-syringe irrigation. In an animal model of heterotopic ossification, 24 Sprague-Dawley rats underwent hindlimb blast amputation via detonation of a submerged explosive, with subsequent through-the-knee surgical amputation proximal to the zone of injury. All wounds were irrigated and underwent primary closure. In 12 of the animals, pulsatile lavage (20 psi [138 kPa]) was used as the irrigation method, and in the other 12 animals, bulb-syringe irrigation was performed. A third group of 6 rats did not undergo the blast procedure but instead underwent surgical incision into the left thigh muscle followed by pulsatile lavage. Serial radiographs of the animals were made to monitor the formation of soft-tissue radiopaque lesions until euthanasia at 6 months. Image-guided muscle biopsies were performed at 8 weeks and 6 months (at euthanasia) on representative animals from each group. Histological analysis was performed with hematoxylin and eosin, alizarin red, and von Kossa staining on interval biopsy and postmortem specimens. All animals managed with pulsatile lavage, with or without blast injury, developed soft-tissue radiopaque lesions, whereas no animal that had bulb-syringe irrigation developed these lesions (p = 0.001). Five of the 12 animals that underwent blast amputation with pulsatile lavage experienced wound complications, whereas no animal in the other 2 groups experienced wound complications (p = 0.014). Radiopaque lesions appeared approximately 10 days postoperatively, increased in density until approximately 16 weeks, then

Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

NARCIS (Netherlands)

N.S. Macklon (Nick); M.J.C. Eijkemans (René); M. Ludwig (Michael); R.E. Felberbaum; K. Diedrich; S. Bustion; E. Loumaye; B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)

2003-01-01

textabstractReplacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because

Sexual dimorphism of gonadotropin-releasing hormone type-III (GnRH3) neurons and hormonal sex reversal of male reproductive behavior in Mozambique tilapia.

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Kuramochi, Asami; Tsutiya, Atsuhiro; Kaneko, Toyoji; Ohtani-Kaneko, Ritsuko

2011-10-01

In tilapia, hormone treatment during the period of sexual differentiation can alter the phenotype of the gonads, indicating that endocrine factors can cause gonadal sex reversal. However, the endocrine mechanism underlying sex reversal of reproductive behaviors remains unsolved. In the present study, we detected sexual dimorphism of gonadotropin-releasing hormone type III (GnRH3) neurons in Mozambique tilapia Oreochromis mossambicus. Our immunohistochemical observations showed sex differences in the number of GnRH3 immunoreactive neurons in mature tilapia; males had a greater number of GnRH3 neurons in the terminal ganglion than females. Treatment with androgen (11-ketotestosterone (11-KT) or methyltestosterone), but not that with 17β-estradiol, increased the number of GnRH3 neurons in females to a level similar to that in males. Furthermore, male-specific nest-building behavior was induced in 70% of females treated with 11-KT within two weeks after the onset of the treatment. These results indicate androgen-dependent regulation of GnRH3 neurons and nest-building behavior, suggesting that GnRH3 is importantly involved in sex reversal of male-specific reproductive behavior.

[EFECTOS NEUROENDOCRINOS DE INSULINA, IGF-I Y LEPTINA SOBRE LA SECRECIÓN DE HORMONA LIBERADORA DE GONADOTROPINAS (GnRH

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Ana Maria Rosales-Torres

2011-10-01

Full Text Available El balance energético del individuo determina en gran medida su eficiencia reproductiva. Bajo condiciones de balance negativo de energía, en la mayoría de los mamíferos, hay una reducción en la síntesis de hormona liberadora de gonadotropinas (GnRH, lo cual disminuye la actividad del eje hipotálamo-hipófisis-gónadas. Cuando el balance energético es revertido, el hipotálamo puede monitorear este cambio y restablecer la secreción de GnRH. La Insulina, el Factor de Crecimiento similar a la Insulina I (IGF-I y Leptina parecen ser los principales mensajeros que informan al hipotálamo sobre el estado energético del animal puesto que las concentraciones periféricas de estas hormonas en situaciones energéticas negativas o positivas, se han asociado con los cambios en la secreción de GnRH. En la presente revisión se muestra como IGF-I actúa directamente sobre neuronas secretoras de GnRH, afectando su síntesis, en tanto que insulina y leptina actúan sobre neuronas en el núcleo arcuato, las cuales hacen sinapsis con neuronas GnRH en el área preóptica medial. Sobre neuronas productoras de neuropéptido Y (NPY insulina y leptina reducen su expresión y por lo tanto el efecto negativo del NPY sobre neuronas GnRH. En cambio insulina y leptina estimulan la síntesis de péptido similar a la galanina (GLAP y propiomelanocortina (POMC. Tanto GALP como los metabolitos de POMC (hormona estimulante de melanocitos principalmente incrementan la síntesis de GnRH. Finalmente, la leptina, incrementa la expresión de kispeptina en neuronas del núcleo ARC. Kispeptina por su parte también tiene un efecto positivo sobre la síntesis y secreción de GnRH.

Augmentative effect of pulsatility on the wall shear stress in tube flow.

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Nakata, M; Tatsumi, E; Tsukiya, T; Taenaka, Y; Nishimura, T; Nishinaka, T; Takano, H; Masuzawa, T; Ohba, K

1999-08-01

Wall shear stress (WSS) has been considered to play an important role in the physiological and metabolic functions of the vascular endothelial cells. We investigated the effects of the pulse rate and the maximum flow rate on the WSS to clarify the influence of pulsatility. Water was perfused in a 1/2 inch transparent straight cylinder with a nonpulsatile centrifugal pump and a pulsatile pneumatic ventricular assist device (VAD). In nonpulsatile flow (NF), the flow rate was changed 1 to 6 L/min by 1 L/min increments to obtain standard values of WSS at each flow rate. In pulsatile flow (PF), the pulse rate was controlled at 40, 60, and 80 bpm, and the maximum flow rate was varied from 3.3 to 12.0 L/min while the mean flow rate was kept at 3 L/min. The WSS was estimated from the velocity profile at measuring points using the laser illuminated fluorescence method. In NF, the WSS was 12.0 dyne/cm2 at 3 L/min and 33.0 dyne/cm2 at 6 L/min. In PF, the pulse rate change with the same mean, and the maximum flow rate did not affect WSS. On the other hand, the increase in the maximum flow rate at the constant mean flow rate of 3 L/min augmented the mean WSS from 13.1 to 32.9 dyne/cm2. We concluded that the maximum flow rate exerted a substantial augmentative effect on WSS, and the maximum flow rate was a dominant factor of pulsatility in this effect.

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

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Rigó János

2009-09-01

Full Text Available Abstract Background Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome. Methods Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI. One hundred combined GnRH agonist + HMG (long protocol cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P Results The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P Conclusion Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.

Return to fertility after extended chemical castration with a GnRH antagonist

International Nuclear Information System (INIS)

Kostanski, Janusz W; Jiang, Ge; Dani, Bhas A; Murty, Santos B; Qiu, Wei; Schrier, Bruce; Thanoo, B C; DeLuca, Patrick P

2001-01-01

Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist

Return to fertility after extended chemical castration with a GnRH antagonist

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Schrier Bruce

2001-10-01

Full Text Available Abstract Background Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. Methods Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days or vehicle alone (control group. Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. Results All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter and control (10.6 offspring per litter were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. Conclusions These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist.

Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization

NARCIS (Netherlands)

B.C.J.M. Fauser (Bart); D. de Jong (Danielle); F. Olivennes; H. Wramsby; C. Tay; J. Itskovitz-Eldor; H.G. van Hooren

2002-01-01

textabstractIn a randomized multicenter study, the efficacies of two different GnRH agonists were compared with that of hCG for triggering final stages of oocyte maturation after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation was conducted by recombinant

Genomic structure and promoter functional analysis of GnRH3 gene in large yellow croaker (Larimichthys crocea).

Science.gov (United States)

Huang, Wei; Zhang, Jianshe; Liao, Zhi; Lv, Zhenming; Wu, Huifei; Zhu, Aiyi; Wu, Changwen

2016-01-15

Gonadotropin-releasing hormone III (GnRH3) is considered to be a key neurohormone in fish reproduction control. In the present study, the cDNA and genomic sequences of GnRH3 were cloned and characterized from large yellow croaker Larimichthys crocea. The cDNA encoded a protein of 99 amino acids with four functional motifs. The full-length genome sequence was composed of 3797 nucleotides, including four exons and three introns. Higher identities of amino acid sequences and conserved exon-intron organizations were found between LcGnRH3 and other GnRH3 genes. In addition, some special features of the sequences were detected in partial species. For example, two specific residues (V and A) were found in the family Sciaenidae, and the unique 75-72 bp type of the open reading frame 2 and 3 existed in the family Cyprinidae. Analysis of the 2576 bp promoter fragment of LcGnRH3 showed a number of transcription factor binding sites, such as AP1, CREB, GATA-1, HSF, FOXA2, and FOXL1. Promoter functional analysis using an EGFP reporter fusion in zebrafish larvae presented positive signals in the brain, including the olfactory region, the terminal nerve ganglion, the telencephalon, and the hypothalamus. The expression pattern was generally consistent with the endogenous GnRH3 GFP-expressing transgenic zebrafish lines, but the details were different. These results indicate that the structure and function of LcGnRH3 are generally similar to the other teleost GnRH3 genes, but there exist some distinctions among them. Copyright © 2015 Elsevier B.V. All rights reserved.

On the pulsatile nature of intracranial and spinal CSF-circulation demonstrated by MR imaging

International Nuclear Information System (INIS)

Greitz, D.; Franck, A.; Nordell, B.

1993-01-01

Cerebrospinal fluid (CSF) flow was studied in 24 healthy volunteers using gated MR phase imaging. The subarachnoid space (SAS) was divided into 5 compartments depending on the magnitude of the pulsatile CSF flows: a high velocity compartment in the area of the brain stem and spinal cord, 2 slow ones at the upper and lower extremes of the SAS, and finally 2 intermediate velocity compartments in between. The main pulsatile spinal flow channel had a meandering pattern. The extraventricular CSF-circulation can be explained by pulsatile CSF flow without the necessity of assuming existence of a net flow. A successive time offset during the cardiac cycle has been found in the fronto-occipital direction of the interplay between the arterial expansion, brain expansion, volume changes of the CSF spaces and of the veins. It is proposed to name this time offset the intracranial ''volume wave'' (VoW). (orig.)

Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse.

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Yip, Siew Hoong; Boehm, Ulrich; Herbison, Allan E; Campbell, Rebecca E

2015-07-01

Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.

Tonsillar pulsatility before and after surgical decompression for children with Chiari malformation type 1: an application for true fast imaging with steady state precession

International Nuclear Information System (INIS)

Radmanesh, Alireza; Greenberg, Jacob K.; Smyth, Matthew D.; Limbrick, David D.; Chatterjee, Arindam; Sharma, Aseem

2015-01-01

We hypothesize that surgical decompression for Chiari malformation type 1 (CM-1) is associated with statistically significant decrease in tonsillar pulsatility and that the degree of pulsatility can be reliably assessed regardless of the experience level of the reader. An Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was performed on 22 children with CM-1 (8 males; mean age 11.4 years) who had cardiac-gated true-FISP sequence and phase-contrast cerebrospinal fluid (CSF) flow imaging as parts of routine magnetic resonance (MR) imaging before and after surgical decompression. The surgical technique (decompression with or without duraplasty) was recorded for each patient. Three independent radiologists with different experience levels assessed tonsillar pulsatility qualitatively and quantitatively and assessed peritonsillar CSF flow qualitatively. Results were analyzed. To evaluate reliability, Fleiss kappa for multiple raters on categorical variables and intra-class correlation for agreement in pulsatility ratings were calculated. After surgical decompression, the degree of tonsillar pulsatility appreciably decreased, confirmed by t test, both qualitatively (p values <0.001, <0.001, and 0.045 for three readers) and quantitatively (amount of decrease/p value for three readers 0.7 mm/<0.001, 0.7 mm/<0.001, and 0.5 mm/0.022). There was a better agreement among the readers in quantitative assessment of tonsillar pulsatility (kappa 0.753-0.834), compared to qualitative assessment of pulsatility (kappa 0.472-0.496) and qualitative assessment of flow (kappa 0.056 to 0.203). Posterior fossa decompression with duraplasty led to a larger decrease in tonsillar pulsatility, compared to posterior fossa decompression alone. Tonsillar pulsatility in CM-1 is significantly reduced after surgical decompression. Quantitative assessment of tonsillar pulsatility was more reliable across readers than

Tonsillar pulsatility before and after surgical decompression for children with Chiari malformation type 1: an application for true fast imaging with steady state precession

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Radmanesh, Alireza [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Washington University School of Medicine, Mallinckrodt Institute of Radiology, St Louis, MO (United States); Greenberg, Jacob K.; Smyth, Matthew D.; Limbrick, David D. [Washington University School of Medicine, Department of Neurosurgery, St Louis, MO (United States); Chatterjee, Arindam; Sharma, Aseem [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St Louis, MO (United States)

2015-04-01

We hypothesize that surgical decompression for Chiari malformation type 1 (CM-1) is associated with statistically significant decrease in tonsillar pulsatility and that the degree of pulsatility can be reliably assessed regardless of the experience level of the reader. An Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was performed on 22 children with CM-1 (8 males; mean age 11.4 years) who had cardiac-gated true-FISP sequence and phase-contrast cerebrospinal fluid (CSF) flow imaging as parts of routine magnetic resonance (MR) imaging before and after surgical decompression. The surgical technique (decompression with or without duraplasty) was recorded for each patient. Three independent radiologists with different experience levels assessed tonsillar pulsatility qualitatively and quantitatively and assessed peritonsillar CSF flow qualitatively. Results were analyzed. To evaluate reliability, Fleiss kappa for multiple raters on categorical variables and intra-class correlation for agreement in pulsatility ratings were calculated. After surgical decompression, the degree of tonsillar pulsatility appreciably decreased, confirmed by t test, both qualitatively (p values <0.001, <0.001, and 0.045 for three readers) and quantitatively (amount of decrease/p value for three readers 0.7 mm/<0.001, 0.7 mm/<0.001, and 0.5 mm/0.022). There was a better agreement among the readers in quantitative assessment of tonsillar pulsatility (kappa 0.753-0.834), compared to qualitative assessment of pulsatility (kappa 0.472-0.496) and qualitative assessment of flow (kappa 0.056 to 0.203). Posterior fossa decompression with duraplasty led to a larger decrease in tonsillar pulsatility, compared to posterior fossa decompression alone. Tonsillar pulsatility in CM-1 is significantly reduced after surgical decompression. Quantitative assessment of tonsillar pulsatility was more reliable across readers than

Does Flexible Arterial Tubing Retain More Hemodynamic Energy During Pediatric Pulsatile Extracorporeal Life Support?

Science.gov (United States)

Wang, Shigang; Kunselman, Allen R; Ündar, Akif

2017-01-01

The objective of this study was to evaluate the hemodynamic performance and energy transmission of flexible arterial tubing as the arterial line in a simulated pediatric pulsatile extracorporeal life support (ECLS) system. The ECLS circuit consisted of a Medos Deltastream DP3 diagonal pump head, Medos Hilite 2400 LT oxygenator, Biomedicus arterial/venous cannula (10 Fr/14 Fr), 3 feet of polyvinyl chloride (PVC) arterial tubing or latex rubber arterial tubing, primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). Trials were conducted at flow rates of 300 to 1200 mL/min (300 mL/min increments) under nonpulsatile and pulsatile modes at 36°C using either PVC arterial tubing (PVC group) or latex rubber tubing (Latex group). Real-time pressure and flow data were recorded using a custom-based data acquisition system. Mean pressures and energy equivalent pressures (EEP) were the same under nonpulsatile mode between the two groups. Under pulsatile mode, EEPs were significantly great than mean pressure, especially in the Latex group (P tubing retained more hemodynamic energy passing through it under pulsatile mode while mean pressures and pressure drops across the ECLS circuit were similar between PVC and latex rubber arterial tubing. Further studies are warranted to verify our findings. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep

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SERGIO E RECABARREN

2007-01-01

Full Text Available Although evidence is accumulating that prenatal testosterone (T compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg, as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01. The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05. AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05. Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring

The use of a combined regimen of GnRH agonist plus a low-dose oral contraceptive improves the spontaneous pulsatile LH secretory characteristics in patients with polycycstic ovary disease after discontinuation of treatment.

Science.gov (United States)

Genazzani, A D; Battaglia, C; Gamba, O; Petraglia, F; Malavasi, B; Genazzani, A R

2000-05-01

The fertility rate in women with polycystic ovary disease (PCOD) is influenced by the type of treatment received. The present study evaluated the possible correlation between treatment and pulsatile release of gonadotropins. Spontaneous episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and hormonal parameters were monitored before and after 1, 3, and 6 months after treatments suspension. Twenty-four PCOD patients were randomly divided into two groups of 12 subjects. Group A was treated with gonadotropin-releasing hormone (GnRH)-analogue plus oral contraceptive (OC). Group B was treated only with OC. Both groups were treated for 6 months and followed up for 6 months. In all subjects the therapeutic regimens reduced the androgenic milieau and the gonadotropin plasma levels. Spontaneous pulsatile secretion of LH and FSH was significantly modified in both groups, but patients who received the combined regimen showed a significantly greater reduction of LH plasma levels and a significantly greater decrease of LH pulse amplitude throughout the 6 months after treatment suspension. Ferriman-Gallway score and ovarian volumes were significantly reduced in patients who received the combined treatment than in the OC-treated patients. These data support the evidence of a higher efficacy of the combination of GnRH-a + OC than OC alone in restoring a normal and adequate spontaneous episodic gonadotropin discharge and in decreasing Ferriman-Gallway score and ovarian volumes in patients with PCOD.

Endocannabinoids and Endovanilloids: A Possible Balance in the Regulation of the Testicular GnRH Signalling

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Rosanna Chianese

2013-01-01

Full Text Available Reproductive functions are regulated both at central (brain and gonadal levels. In this respect, the endocannabinoid system (eCS has a very influential role. Interestingly, the characterization of eCS has taken many advantages from the usage of animal models different from mammals. Therefore, this review is oriented to summarize the main pieces of evidence regarding eCS coming from the anuran amphibian Rana esculenta, with particular interest to the morphofunctional relationship between eCS and gonadotropin releasing hormone (GnRH. Furthermore, a novel role for endovanilloids in the regulation of a testicular GnRH system will be also discussed.

Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction.

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Wu, Min; Dumalska, Iryna; Morozova, Elena; van den Pol, Anthony; Alreja, Meenakshi

2009-10-06

A link between energy balance and reproduction is critical for the survival of all species. Energy-consuming reproductive processes need to be aborted in the face of a negative energy balance, yet knowledge of the pathways mediating this link remains limited. Fasting and food restriction that inhibit fertility also upregulate the hypothalamic melanin-concentrating hormone (MCH) system that promotes feeding and decreases energy expenditure; MCH knockout mice are lean and have a higher metabolism but remain fertile. MCH also modulates sleep, drug abuse behavior, and mood, and MCH receptor antagonists are currently being developed as antiobesity and antidepressant drugs. Despite the clinical implications of MCH, the direct postsynaptic effects of MCH have never been reported in CNS neurons. Using patch-clamp recordings in brain slices from multiple lines of transgenic GFP mice, we demonstrate a strong inhibitory effect of MCH on an exclusive population of septal vGluT2-GnRH neurons that is activated by the puberty-triggering and preovulatory luteinizing hormone surge-mediating peptide, kisspeptin. MCH has no effect on kisspeptin-insensitive GnRH, vGluT2, cholinergic, or GABAergic neurons located within the same nucleus. The inhibitory effects of MCH are reproducible and nondesensitizing and are mediated via a direct postsynaptic Ba(2+)-sensitive K(+) channel mechanism involving the MCHR1 receptor. MCH immunoreactive fibers are in close proximity to vGluT2-GFP and GnRH-GFP neurons. Importantly, MCH blocks the excitatory effect of kisspeptin on vGluT2-GnRH neurons. Considering the role of MCH in regulating energy balance and of GnRH and kisspeptin in triggering puberty and maintaining fertility, MCH may provide a critical link between energy balance and reproduction directly at the level of the kisspeptin-activated vGluT2-GnRH neuron.

Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

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Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

2013-07-01

The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

Kisspeptin as a master player in the central control of reproduction in mammals: an overview of kisspeptin research in domestic animals.

Science.gov (United States)

Okamura, Hiroaki; Yamamura, Takashi; Wakabayashi, Yoshihiro

2013-05-01

The hypothalamo-pituitary-gonadal (HPG) axis is the regulatory system for reproduction in mammals. Because secretion of gonadotropin-releasing hormone (GnRH) into the portal vessels is the final step at which the brain controls gonadal activities, the GnRH neuronal system had been thought to be central to the HPG axis. A newly discovered neural peptide, kisspeptin, has opened a new era in reproductive neuroendocrinology. As shown in a variety of mammals, kisspeptin is a potent endogenous secretagogue of GnRH, and the kisspeptin neuronal system governs both the pulsatile GnRH secretion that drives folliculogenesis, spermatogenesis and steroidogenesis, and the GnRH surge that triggers ovulation in females. The kisspeptin neuronal system is therefore considered a master player in the central control of mammalian reproduction, and kisspeptin and related substances could therefore be valuable for the development of novel strategies for the management of fertility in farm animals. To this end, the present review aimed to summarize the current research on kisspeptin signaling with a focus on domestic animals such as sheep, goats, cattle, pigs and horses. © 2013 Japanese Society of Animal Science.

Tissue Doppler Imaging in the evaluation of abdominal aortic pulsatility: a useful tool for the neonatologist.

Science.gov (United States)

Valerio, Enrico; Grison, Alessandra; Capretta, Anna; Golin, Rosanna; Ferrarese, Paola; Bellettato, Massimo

2017-03-01

Sonographic cardiac evaluation of newborns with suspected aortic coarctation (AoC) should tend to demonstrate a good phasic and pulsatile flow and the absence of pressure gradient along a normally conformed aortic arch from the modified left parasternal and suprasternal echocardiographic views; these findings, however, may not necessarily rule out a more distal coarctation in the descending aorta. For this reason, the sonographic exam of newborns with suspected AoC should always include a Doppler evaluation of abdominal aortic blood flow from the subcostal view. Occasionally, however, a clearly pulsatile Doppler flow trace in abdominal aorta may be difficult to obtain due to the bad insonation angle existing between the probe and the vessel. In such suboptimal ultrasonic alignment situation, the use of Tissue Doppler Imaging instead of classic Doppler flow imaging may reveal a preserved aortic pulsatility by sampling the aortic wall motion induced by normal flow. We propose to take advantage of the TDI pattern as a surrogate of a normal pulsatile Doppler flow trace in abdominal aorta when the latter is difficult to obtain due to malalignment with the insonated vessel.

Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.

Science.gov (United States)

Roland, Alison V; Moenter, Suzanne M

2011-02-01

Prenatal androgenization (PNA) of female mice with dihydrotestosterone programs reproductive dysfunction in adulthood, characterized by elevated luteinizing hormone levels, irregular estrous cycles, and central abnormalities. Here, we evaluated activity of GnRH neurons from PNA mice and the effects of in vivo treatment with metformin, an activator of AMP-activated protein kinase (AMPK) that is commonly used to treat the fertility disorder polycystic ovary syndrome. Estrous cycles were monitored in PNA and control mice before and after metformin administration. Before metformin, cycles were longer in PNA mice and percent time in estrus lower; metformin normalized cycles in PNA mice. Extracellular recordings were used to monitor GnRH neuron firing activity in brain slices from diestrous mice. Firing rate was higher and quiescence lower in GnRH neurons from PNA mice, demonstrating increased GnRH neuron activity. Metformin treatment of PNA mice restored firing activity and LH to control levels. To assess whether AMPK activation contributed to the metformin-induced reduction in GnRH neuron activity, the AMPK antagonist compound C was acutely applied to cells. Compound C stimulated cells from metformin-treated, but not untreated, mice, suggesting that AMPK was activated in GnRH neurons, or afferent neurons, in the former group. GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose. These studies indicate that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by metformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome.

Precise position control of a helical magnetic robot in pulsatile flow using the rotating frequency of the external magnetic field

Directory of Open Access Journals (Sweden)

Jongyul Kim

2017-05-01

Full Text Available We propose a position control method for a helical magnetic robot (HMR that uses the rotating frequency of the external rotating magnetic field (ERMF to minimize the position fluctuation of the HMR caused by pulsatile flow in human blood vessels. We prototyped the HMR and conducted several experiments in pseudo blood vessel environments with a peristaltic pump. We experimentally obtained the relation between the flow rate and the rotating frequency of the ERMF required to make the HMR stationary in a given pulsatile flow. Then we approximated the pulsatile flow by Fourier series and applied the required ERMF rotating frequency to the HMR in real time. Our proposed position control method drastically reduced the position fluctuation of the HMR under pulsatile flow.

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

Science.gov (United States)

Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

2012-10-01

Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

Stability of Carotid Artery Under Steady-State and Pulsatile Blood Flow: A Fluid–Structure Interaction Study

Science.gov (United States)

Saeid Khalafvand, Seyed; Han, Hai-Chao

2015-01-01

It has been shown that arteries may buckle into tortuous shapes under lumen pressure, which in turn could alter blood flow. However, the mechanisms of artery instability under pulsatile flow have not been fully understood. The objective of this study was to simulate the buckling and post-buckling behaviors of the carotid artery under pulsatile flow using a fully coupled fluid–structure interaction (FSI) method. The artery wall was modeled as a nonlinear material with a two-fiber strain-energy function. FSI simulations were performed under steady-state flow and pulsatile flow conditions with a prescribed flow velocity profile at the inlet and different pressures at the outlet to determine the critical buckling pressure. Simulations were performed for normal (160 ml/min) and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch ratios to determine the effects of flow rate and axial tension on stability. The results showed that an artery buckled when the lumen pressure exceeded a critical value. The critical mean buckling pressure at pulsatile flow was 17–23% smaller than at steady-state flow. For both steady-state and pulsatile flow, the high flow rate had very little effect (<5%) on the critical buckling pressure. The fluid and wall stresses were drastically altered at the location with maximum deflection. The maximum lumen shear stress occurred at the inner side of the bend and maximum tensile wall stresses occurred at the outer side. These findings improve our understanding of artery instability in vivo. PMID:25761257

Stability of carotid artery under steady-state and pulsatile blood flow: a fluid-structure interaction study.

Science.gov (United States)

Saeid Khalafvand, Seyed; Han, Hai-Chao

2015-06-01

It has been shown that arteries may buckle into tortuous shapes under lumen pressure, which in turn could alter blood flow. However, the mechanisms of artery instability under pulsatile flow have not been fully understood. The objective of this study was to simulate the buckling and post-buckling behaviors of the carotid artery under pulsatile flow using a fully coupled fluid-structure interaction (FSI) method. The artery wall was modeled as a nonlinear material with a two-fiber strain-energy function. FSI simulations were performed under steady-state flow and pulsatile flow conditions with a prescribed flow velocity profile at the inlet and different pressures at the outlet to determine the critical buckling pressure. Simulations were performed for normal (160 ml/min) and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch ratios to determine the effects of flow rate and axial tension on stability. The results showed that an artery buckled when the lumen pressure exceeded a critical value. The critical mean buckling pressure at pulsatile flow was 17-23% smaller than at steady-state flow. For both steady-state and pulsatile flow, the high flow rate had very little effect (<5%) on the critical buckling pressure. The fluid and wall stresses were drastically altered at the location with maximum deflection. The maximum lumen shear stress occurred at the inner side of the bend and maximum tensile wall stresses occurred at the outer side. These findings improve our understanding of artery instability in vivo.

High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

Science.gov (United States)

Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

2016-01-01

Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

Association between the extent of sigmoid sinus dehiscence and an occurrence of pulsatile tinnitus: a retrospective imaging study

International Nuclear Information System (INIS)

Dong, C.; Zhao, P.; Liu, Z.; Xu, W.; Lv, H.; Pang, S.; Wang, Z.

2016-01-01

Aim: To assess the extent of sigmoid sinus dehiscence (SSD) on high-resolution computed tomography venography (HRCTV) or high-resolution computed tomography (HRCT) images in pulsatile tinnitus (PT) and non-PT groups to determine whether there is an association between the extent of SSD and occurrence of PT. Materials and methods: Twenty-eight SSD patients with ipsilateral PT and 28 age- and gender-matched SSD patients without PT who underwent HRCTV or HRCT were enrolled in this study and categorised into two groups: “PT group” and “non-PT group”. The extent of SSD in each group was calculated and compared. Results: The largest transverse diameter and largest vertical diameter of SSD in the PT group were 6.21±1.7 and 6.15±2.19 mm, respectively. The largest transverse diameter and largest vertical diameter of SSD in the non-PT group were 3.06±1.38 and 2.51±1.03 mm, respectively. The extent of SSD was statistically different between the two groups (p<0.001; p<0.001). Conclusions: As a cause of PT, SSD can also occur in individuals without PT symptoms. Preliminary findings suggest that there may be a potential correlation between the extent of SSD and an occurrence of PT. - Highlights: • We compared the extent of sigmoid sinus dehiscence in pulsatile tinnitus and non-pulsatile tinnitus groups. • The sigmoid sinus dehiscence in the pulsatile tinnitus patients was larger than those in non-pulsatile tinnitus patients. • There may be a potential correlation between the extent of sigmoid sinus dehiscence and an occurrence of pulsatile tinnitus.

Nonlinear dynamics of shells conveying pulsatile flow with pulse-wave propagation. Theory and numerical results for a single harmonic pulsation

Science.gov (United States)

Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

2017-05-01

In deformable shells conveying pulsatile flow, oscillatory pressure changes cause local movements of the fluid and deformation of the shell wall, which propagate downstream in the form of a wave. In biomechanics, it is the propagation of the pulse that determines the pressure gradient during the flow at every location of the arterial tree. In this study, a woven Dacron aortic prosthesis is modelled as an orthotropic circular cylindrical shell described by means of the Novozhilov nonlinear shell theory. Flexible boundary conditions are considered to simulate connection with the remaining tissue. Nonlinear vibrations of the shell conveying pulsatile flow and subjected to pulsatile pressure are investigated taking into account the effects of the pulse-wave propagation. For the first time in literature, coupled fluid-structure Lagrange equations of motion for a non-material volume with wave propagation in case of pulsatile flow are developed. The fluid is modeled as a Newtonian inviscid pulsatile flow and it is formulated using a hybrid model based on the linear potential flow theory and considering the unsteady viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. Contributions of pressure and velocity propagation are also considered in the pressure drop along the shell and in the pulsatile frictional traction on the internal wall in the axial direction. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior of a pressurized Dacron aortic graft conveying blood flow. A pulsatile time-dependent blood flow model is considered by applying the first harmonic of the physiological waveforms of velocity and pressure during the heart beating period. Geometrically nonlinear vibration response to pulsatile flow and transmural pulsatile pressure, considering the propagation of pressure and velocity changes inside the shell, is here presented via frequency-response curves, time histories, bifurcation

Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients

DEFF Research Database (Denmark)

Polyzos, Nikolaos P; Devos, Michel; Humaidan, Peter

2013-01-01

OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria...... developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated...

Estimating right ventricular stroke work and the pulsatile work fraction in pulmonary hypertension.

Science.gov (United States)

Chemla, Denis; Castelain, Vincent; Zhu, Kaixian; Papelier, Yves; Creuzé, Nicolas; Hoette, Susana; Parent, Florence; Simonneau, Gérald; Humbert, Marc; Herve, Philippe

2013-05-01

The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW. Eleven patients with severe, precapillary pulmonary hypertension (PH) (six patients with idiopathic pulmonary arterial hypertension and five with chronic thromboembolic PH; mPAP = 57 ± 10 mm Hg) were studied at rest and during mild to moderate exercise. Eight non-PH control subjects were also studied at rest (mPAP = 16 ± 2 mm Hg). The msePAP was averaged from end diastole to dicrotic notch. In the full data set (53 pressure-flow points), mPAP ranged from 14 to 99.5 mm Hg, cardiac output from 2.38 to 11.1 L/min, and heart rate from 53 to 163 beats/min. There was a linear relationship between msePAP and mPAP (r² = 0.99). The msePAP matched 1.25 mPAP (bias, -0.5 ± 2.6 mm Hg). Results were similar in the resting non-PH group and in resting and the exercising PH group. This implies that the classic formula markedly underestimates RVSW and that the pulsatile work may be a variable 20% to 55% fraction of RVSW, depending on RAP and mPAP. At rest, RVSW in patients with PH was twice as high as that of the non-PH group (P work fraction was similar between the two groups (26 ± 4% vs 24 ± 1%) because of the counterbalancing effects of high RAP (11 ± 5 mm Hg vs 4 ± 2 mm Hg), which increases the fraction, and high mPAP, which decreases the fraction. Our study favored the use of an improved formula that takes into account the variable pulsatile work fraction: RVSW = (1.25 mPAP - RAP) × stroke volume. Increased RAP and increased mPAP have opposite effects on the pulsatile work

Circadian Control of the Estrogenic Circuits Regulating GnRH Secretion and the Preovulatory Luteinizing Hormone Surge

Directory of Open Access Journals (Sweden)

Lance J Kriegsfeld

2012-05-01

Full Text Available Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG axis functioning. In mammals, the master circadian pacemaker in the suprachaismatic nucleus (SCN of the anterior hypothalamus coordinates reproductively-relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the GnRH system in control of the preovulatory LH surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility.

Science.gov (United States)

Ng, Boon C; Kleinheyer, Matthias; Smith, Peter A; Timms, Daniel; Cohn, William E; Lim, Einly

2018-01-01

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9-15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.

A durability study of a paracorporeal pulsatile electro-mechanical pneumatic biventricular assist device.

Science.gov (United States)

Choi, Hyuk; Lee, Heung-Man; Nam, Kyoung Won; Choi, Jaesoon; Lee, Jung-Joo; Kim, Ho Chul; Song, Seung Joon; Ahn, Chi Bum; Son, Ho Sung; Lim, Choon Hak; Son, Kuk Hui; Park, Yong Doo; Jeong, Gi Seok; Sun, Kyung

2011-06-01

In 2002, the paracorporeal pulsatile electro-mechanical pneumatic ventricular assist device (VAD) began to be developed by the Korea Artificial Organ Center at Korea University under a Health & Medical Technology Research and Development program which finished in 2008. In vitro durability testing was conducted on the paracorporeal pulsatile pneumatic VAD to determine device durability and to evaluate device failures. The 1- and 2-year reliability of the paracorporeal pulsatile pneumatic VAD was shown to be 91.2% and 54.9%, respectively, with an 80% confidence level. Failure modes were analyzed using fault tree analysis, with customized software continuously acquiring data during the test period. After this period, 21 in vivo animal tests were done, with 14 cases of left atrium to left ventricle (LV) inflow cannulation (36Fr)/outflow grafting to descending aorta, and seven cases of apex cannulation of LV to descending aorta (12 mm). The longest postoperative day (182 days) in Korea was recently recorded in in vivo animal testing (bovine, 90 kg, male, 3.5-4.0 L/min flow rate, and 55 bpm). © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine.

Science.gov (United States)

Wang, Yiqin; Alahdal, Murad; Ye, Jia; Jing, Liangliang; Liu, Xiaoxin; Chen, Huan; Jin, Liang; Cao, Rongyue

2018-01-23

GnRH and VEGF have been investigated as prostate carcinoma enhancers that support tumor spread and progression. Although both have documented roles in prostate carcinoma and many cancer types, the weak immunogenicity of these peptides has remained a major challenge for use in immunotherapy. Here, we describe a novel strategy to inhibit GnRH and VEGF production and assess the effect on the immune responses against these hormones using the RM-1 prostate cancer model. We designed a novel recombinant fusion protein which combined GnRH and VEGF as a vaccine against this tumor. The newly constructed fusion protein hVEGF121-M2-GnRH3-hinge-MVP contains the human vascular endothelial growth factor (hVEGF121) and three copies of GnRH in sequential linear alignment and T helper epitope MVP as an immunogenic vaccine. The effectiveness of the vaccine in eliciting an immune response and attenuating the prostate tumor growth was evaluated. Results showed that administration of a new vaccine effectively elicited humoral and cellular immune responses. We found that, a novel fusion protein, hVEGF121-M2-GnRH3-hinge-MVP, effectively inhibited growth of RM-1 prostate model and effectively promoted immune response. In conclusion, hVEGF121-M2-GnRH3-hinge-MVP is an effective dual mechanism tumor vaccine that limits RM-1 prostate growth. This vaccine may be a promising strategy for the treatment of hormone refractory prostate malignancies.

The Effect of a GnRH Agonist Injection or Progesterone Implant at Diestrus in Cryopreserved Embryo Transferred Cows

OpenAIRE

KIRBAŞ, Mesut; BÜLBÜL, Bülent; KÖSE, Mehmet; DURSUN, Şükrü; ÇOLAK, Mehmet

2014-01-01

In this study, the effect of a single dose of GnRH on d 13 or progesterone implant for 7 days between d 13 and 20 on plasma progesterone levels and pregnancy rates on cryopreserved embryo transferred cows were investigated. Synchronized 48 Brown Swiss recipient cows were used as animal material. Seven days after estrus detection, cryopreserved cattle embryos were transferred into recipients and cows were assigned randomly into three groups. In GnRH group (n=16), cows were intramuscularly inje...

Obstructive Hydrocephalus Secondary to Enlarged Virchow-Robin Spaces: A Rare Cause of Pulsatile Tinnitus.

Science.gov (United States)

Donaldson, Christopher; Chatha, Gurkirat; Chandra, Ronil V; Goldschlager, Tony

2017-05-01

Obstructive hydrocephalus secondary to enlarged Virchow-Robin Spaces (VRS) is a rare entity, with only a few cases reported in the literature. Presenting symptoms vary widely from headaches to dizziness. We report a case of a 31-year-old man who presented with pulsatile tinnitus and magnetic resonance imaging showing obstructive hydrocephalus secondary to tumefactive VRS. After a cerebrospinal fluid diversion procedure in the form of an endoscopic third ventriculostomy, he had almost complete resolution of his symptoms. This is the first case of obstructive hydrocephalus secondary to enlarged VRS, presenting with pulsatile tinnitus. Copyright © 2017 Elsevier Inc. All rights reserved.

Hormonal responses to GnRH injection given at different stages of ...

African Journals Online (AJOL)

USER

2010-04-05

Apr 5, 2010 ... In conclusion, the results presented here indicate that. GnRH given at the beginning (days 5 to 7) or at the end. (days 15 to 17) of the estrous cycle did not alter the profile of progesterone and estradiol concentration in water buffaloes as previously described in cattle (Kohram et al., 1998a, b). REFERENCES.

Pulsatile dry cupping in chronic low back pain - a randomized three-armed controlled clinical trial.

Science.gov (United States)

Teut, M; Ullmann, A; Ortiz, M; Rotter, G; Binting, S; Cree, M; Lotz, F; Roll, S; Brinkhaus, B

2018-04-02

We aimed to investigate the effectiveness of two different forms of dry pulsatile cupping in patients with chronic low back pain (cLBP) compared to medication on demand only in a three-armed randomized trial. 110 cLBP patients were randomized to regular pulsatile cupping with 8 treatments plus paracetamol on demand (n = 37), minimal cupping with 8 treatments plus paracetamol on demand (n = 36) or the control group with paracetamol on demand only (n = 37). Primary outcome was the pain intensity on a visual analogue scale (VAS, 0-100 mm) after 4 weeks, secondary outcome parameter included VAS pain intensity after 12 weeks, back function as measured with the 'Funktionsfragebogen Hannover Rücken' (FFbH-R) and health related quality of life questionnaire Short form 36 (SF-36) after 4 and 12 weeks. The mean baseline-adjusted VAS after 4 weeks was 34.9 mm (95% CI: 28.7; 41.2) for pulsatile cupping, 40.4 (34.2; 46.7) for minimal cupping and 56.1 (49.8; 62.4) for control group, resulting in statistically significant differences between pulsatile cupping vs. control (21.2 (12.2; 30.1); p back function after 4 weeks, but not after 12 weeks (- 5.4 (- 11.7;0.8); p = 0.088), pulsatile cupping also showed better improvements on SF-36 physical component scale compared to control at 4 and 12 weeks (- 5.6 (- 9.3;-2.0); p = 0.003; - 6.1 (- 9.9;-2.4); p = 0.002). For back function and quality of life minimal cupping group was not statistically different to control after 4 and 12 weeks. Paracetamol intake did not differ between the groups (cupping vs. control (7.3 (- 0.4;15.0); p = 0.063); minimal cupping vs. control (6.3 (- 2.0;14.5); p = 0.133). Both forms of cupping were effective in cLBP without showing significant differences in direct comparison after four weeks, only pulsatile cupping showed effects compared to control after 12 weeks. The study was registered at ClinicalTrials.gov (identifier: NCT02090686 ).

Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge

DEFF Research Database (Denmark)

Williams, Wilbur P; Jarjisian, Stephan G; Mikkelsen, Jens D

2011-01-01

In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit...... linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic...... of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control....

Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

Directory of Open Access Journals (Sweden)

Checa MA

2015-02-01

Full Text Available Miguel A Checa,1,2 Mario Brassesco,2 Margalida Sastre,1 Manuel Gómez,2 Julio Herrero,3 Laura Marque,3 Arturo Brassesco,2 Juan José Espinós3 1Department of Obstetrics and Gynecology, Parc de Salut Mar, Universitat Autònoma de Barcelona, 2Centro de Infertilidad y Reproducción Humana (CIRH, 3Centro de Reproducción Asistida Sagrada Familia, Clínica Sagrada Familia, Barcelona, Spain Abstract: The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332 was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B or on day 20 (protocol C of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A. The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation. The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase and C (stimulation on luteal phase were compared with protocol A (standard stimulation. GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency

Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

International Nuclear Information System (INIS)

Lee, Kyung Soon; Woo, Bock Hi

2001-01-01

To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Soon; Woo, Bock Hi [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

2001-06-15

To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

Induction of Gonadotropins for Reproductive Control

Directory of Open Access Journals (Sweden)

Elza Ibrahim Auerkari

2015-10-01

Full Text Available Much of the recent research on gonadotropin – related control processes of reproduction and reproductive maturation has concentrated on the neuronal and molecular biology of gonadotropin release. The reproductive development of healthy mammals requires appropriate fetal develompment and migration of the neural network controlling and including the gonadotropin releasing hormone (GnRH – producing neurons that are needed to regulate GnRH and luteinizing hormone (LH release. GnRH is also necessary for the development of the gonadotropin – producing pituitary gland. The fetal gonads respon to GnRH – induced LH production by producing the gonadal steroids required for further reproductive differentiation. Pubertal maturation is characterised by increases in LH levels, representing the corresponding pulsatile release of GnRH. This GnRH pulse generator appears to be an intrinsic property of the arcuate nucleus at the medial basal hypothalamus. The generator activity can be mediated by the neurotransmitter aspartate which activates neurons of the hypothalamus, inducing acuate releases of GnRH and hence initiates puberty. A major factor in human reproductive maturation is the decrease in the age of puberty, caused by improvement of nutritional conditions due to the socio – economic development. This implies that the pubertal activation of GnRH secretion depends on metabolic conditions. Of the substances that mediate the metabolic condition to the neuronal network regulating GnRH secretion, the role of the neuropeptide Y (NPY appears instrumental : for healthy mammals less food means more NPY, and accumulated NPY makes food to become sex. NPY does this by regulating the appropriate hypothalamic functions including the neuroendocrine control of gonadotropin release.

Leaback of Pulsatile Flow of Particle Fluid Suspension Model of ...

African Journals Online (AJOL)

Leaback of Pulsatile Flow of Particle Fluid Suspension Model of Blood Under Periodic Body Acceleration. ... The variation in body acceleration amplitude though affects the velocity profile in the capillary tubes, it has no effect on the leakback in the tubes. Leakback is mainly determined by the balance of the viscous drag and ...

A study of doppler waveform using pulsatile flow model

International Nuclear Information System (INIS)

Chung, Hye Won; Chung, Myung Jin; Park, Jae Hyung; Chung, Jin Wook; Lee, Dong Hyuk; Min, Byoung Goo

1997-01-01

Through the construction of a pulsatile flow model using an artificial heart pump and stenosis to demonstrate triphasic Doppler waveform, which simulates in vivo conditions, and to evaluate the relationship between Doppler waveform and vascular compliance. The flow model was constructed using a flowmeter, rubber tube, glass tube with stenosis, and artificial heart pump. Doppler study was carried out at the prestenotic, poststenotic, and distal segments;compliance was changed by changing the length of the rubber tube. With increasing proximal compliance, Doppler waveforms show decreasing peak velocity of the first phase and slightly delayed acceleration time, but the waveform itself did not change significantly. Distal compliance influenced the second phase, and was important for the formation of pulsus tardus and parvus, which without poststenotic vascular compliance, did not develop. The peak velocity of the first phase was inversely proportional to proximal compliance, and those of the second and third phases were directly proportional to distal compliance. After constructing this pulsatile flow model, we were able to explain the relationship between vascular compliance and Doppler waveform, and also better understand the formation of pulsus tardus and parvus

The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS).

Science.gov (United States)

Lewandowski, Krzysztof C; Cajdler-Łuba, Agata; Salata, Ireneusz; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS. The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test. Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p 2.11 or LH(₆₀ min)/FSH(₆₀ min) > 1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for the diagnosis of PCOS, respectively. Women with PCOS have higher baseline and GnRH-stimulated LH concentrations. GnRH stimulation results in an increase in LH/FSH ratio in women with PCOS. Therefore we postulate that this phenomenon might be potentially useful as an additional tool in the diagnosis of PCOS.

Synchronisation of the follicular wave with GnRH and PGF2α analogue for a timed breeding programme in dromedary camels (Camelus dromedarius).

Science.gov (United States)

Manjunatha, B M; Al-Bulushi, Samir; Pratap, N

2015-09-01

This study was conducted to develop a hormone protocol that precisely synchronises follicular development for a timed breeding (TB) programme in dromedary camels. To examine the effect of GnRH treatment at four known stages of follicular development, animals were treated with GnRH when the largest follicle of the wave was 4-7, 8-11, 12-17 and 18-27 mm in diameter. Transrectal ultrasonography was carried out daily up to 20 days after treatment. A hormone protocol (FWsynch) for the synchronisation of follicular wave and TB consisting of GnRH-1 (GnRH) on Day 0, PG-1 (PGF2α) on Day 7, GnRH-2 on Day 10 and PG-2 on Day 17 was initiated at four known stages of follicular development. Ovarian structures were monitored by ultrasonography. The FWsynch protocol was initiated at random stages of follicle development and animals were bred by natural mating at a fixed time at the research facility and in field. The pregnancy was diagnosed by ultrasonography. GnRH treatment in animals with a dominant follicle (DF) of ≥ 11 mm in diameter resulted in synchronous new follicular wave emergence, whereas in animals with a DF ≤ 10 mm, the treatment did not alter the development of the existing follicular wave. The FWsynch protocol was effective in synchronising the follicular wave for TB irrespective of the stage of follicular development at the beginning of the protocol. TB using FWsynch protocol resulted in a pregnancy rate of 60.2% in a research facility and 53.6% and 45.6% in normal and infertile camels respectively under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

Science.gov (United States)

Yang, Yao-Yao; Liu, Zhe-Peng; Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)-DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP-DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis.

Science.gov (United States)

Sharzehee, Mohammadali; Khalafvand, Seyed Saeid; Han, Hai-Chao

2018-02-01

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.

Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH

DEFF Research Database (Denmark)

Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.

1999-01-01

To use peptides as synthetic vaccines, they have to be coupled to a carrier protein to make them more immunogenic. Coupling efficiency between a carrier protein and a peptide, however, is difficult to control with respect to loading density of the peptide, This makes these carrier proteins poorly...... for the induction of antibodies against GnRH and immunocastration of pigs....

Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

Science.gov (United States)

Dulka, Eden A; Moenter, Suzanne M

2017-11-01

Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

Induction of pulsatile secretion of leptin in horses following thyroidectomy.

Science.gov (United States)

Buff, Preston R; Messer, Nat T; Cogswell, Andria M; Wilson, David A; Johnson, Philip J; Keisler, Duane H; Ganjam, Venkataseshu K

2007-02-01

Endocrine characteristics of Quarter Horse-type mares were determined during a 68 h feed deprivation and again in the same mares following surgical thyroidectomy (THX). A crossover experimental design was implemented, in which mares received brome hay available ad libitum (FED) or were food deprived (RES) for 68 h. Blood samples were collected every 20 min for 48 h, beginning 20 h after the onset of food deprivation. Concentrations of triiodothyronine and thyroxine were undetectable post-THX. Plasma concentrations of thyrotropin were greater post-THX versus pre-THX (P<0 x 001). Plasma concentrations of leptin were greater in the THX FED group than in the THX RES group (P<0 x 01). The existence of leptin pulse secretion was found only in post-THX compared with the same horses pre-THX (P=0 x 02). We theorize that non-pulsatile secretion of leptin may have contributed to the survival of this species, as it evolved in the regions of seasonal availability of food. Lack of pulsatile secretion of leptin may contribute to the accumulation of energy stores by modulating leptin sensitivity.

Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

Science.gov (United States)

Mitchell, Gary F; van Buchem, Mark A; Sigurdsson, Sigurdur; Gotal, John D; Jonsdottir, Maria K; Kjartansson, Ólafur; Garcia, Melissa; Aspelund, Thor; Harris, Tamara B; Gudnason, Vilmundur; Launer, Lenore J

2011-11-01

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, Pwave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, Pwave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, Pwave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, Pwave

Pulsatile turbulent flow through pipe bends at high Dean and Womersley numbers

Science.gov (United States)

Kalpakli, Athanasia; Örlü, Ramis; Tillmark, Nils; Alfredsson, P. Henrik

2011-12-01

Turbulent pulsatile flows through pipe bends are prevalent in internal combustion engine components which consist of bent pipe sections and branching conduits. Nonetheless, most of the studies related to pulsatile flows in pipe bends focus on incompressible, low Womersley and low Dean number flows, primarily because they aim in modeling blood flow, while internal combustion engine related flows have mainly been addressed in terms of integral quantities and consist of single point measurements. The present study aims at bridging the gap between these two fields by means of time-resolved stereoscopic particle image velocimetry measurements in a pipe bend with conditions that are close to those encountered in exhaust manifolds. The time/phase-resolved three-dimensional cross-sectional flow-field 3 pipe diameters downstream the pipe bend is captured and the interplay between different secondary motions throughout a pulse cycle is discussed.

Pulsatile turbulent flow through pipe bends at high Dean and Womersley numbers

International Nuclear Information System (INIS)

Kalpakli, Athanasia; Örlü, Ramis; Tillmark, Nils; Alfredsson, P Henrik

2011-01-01

Turbulent pulsatile flows through pipe bends are prevalent in internal combustion engine components which consist of bent pipe sections and branching conduits. Nonetheless, most of the studies related to pulsatile flows in pipe bends focus on incompressible, low Womersley and low Dean number flows, primarily because they aim in modeling blood flow, while internal combustion engine related flows have mainly been addressed in terms of integral quantities and consist of single point measurements. The present study aims at bridging the gap between these two fields by means of time-resolved stereoscopic particle image velocimetry measurements in a pipe bend with conditions that are close to those encountered in exhaust manifolds. The time/phase-resolved three-dimensional cross-sectional flow-field 3 pipe diameters downstream the pipe bend is captured and the interplay between different secondary motions throughout a pulse cycle is discussed.

The potential for castration of domestic animals by active immunization against GnRH

International Nuclear Information System (INIS)

Gonzalez, A.; Allen, A.F.; Murphy, B.D.; Mapletoft, R.J.; Cohen, R.

1990-01-01

Trials have been carried out in sheep and beef cattle in attempts to induce immunity against gonadotropin releasing hormone (GnRH), with the objective of using immunocastration as a replacement for surgical castration. Of the protein carriers used, ovalbumin and horse albumin yielded highest responses, with keyhole limpet haemocyanin (KLH) being a potent substitute for both. Different adjuvants were also used. In these trials, highest titre responses were obtained using Freund's complete (FCA) or Freund's incomplete (FIA) adjuvant in cattle and sheep. Although no adjuvant was found to yield as high a response as FCA and Alhydrogel, an aluminium hydroxide adjuvant generally yielded a high response in cattle and sheep. The results from the trials in beef calves indicate that active immunization against GnRH does not affect average daily gains, total body weight gain or carcass dressing percentage. The results suggest the potential of immunocastration as a substitute for surgical castration in cattle and sheep. (author). 30 refs, 8 figs, 2 tabs

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

Science.gov (United States)

Gohean, Jeffrey R; George, Mitchell J; Pate, Thomas D; Kurusz, Mark; Longoria, Raul G; Smalling, Richard W

2013-01-01

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Differentially expressed miRNAs after GnRH treatment and their potential roles in FSH regulation in porcine anterior pituitary cell.

Directory of Open Access Journals (Sweden)

Rui-Song Ye

Full Text Available Hypothalamic gonadotropin-releasing hormone (GnRH is a major regulator of follicle-stimulating hormone (FSH secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs are small RNA molecules that control gene expression by imperfect binding to the 3'-untranslated region (3'-UTR of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSHβ mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR. Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSHβ mRNA 3'-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

Science.gov (United States)

Vemula, Sateesh Kumar

2015-12-01

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Pulsatile fluidic pump demonstration and predictive model application

International Nuclear Information System (INIS)

Morgan, J.G.; Holland, W.D.

1986-04-01

Pulsatile fluidic pumps were developed as a remotely controlled method of transferring or mixing feed solutions. A test in the Integrated Equipment Test facility demonstrated the performance of a critically safe geometry pump suitable for use in a 0.1-ton/d heavy metal (HM) fuel reprocessing plant. A predictive model was developed to calculate output flows under a wide range of external system conditions. Predictive and experimental flow rates are compared for both submerged and unsubmerged fluidic pump cases

Secondary flow structures in a 180∘ elastic curved vessel with torsion under steady and pulsatile inflow conditions

Science.gov (United States)

Najjari, Mohammad Reza; Plesniak, Michael W.

2017-11-01

Secondary flow vortical structures were investigated in an elastic 180° curved pipe with and without torsion under steady and pulsatile flow using particle image velocimetry (PIV). The elastic thin-walled curved pipes were constructed using Sylgard 184, and inserted into a bath of refractive index matched fluid to perform PIV. A vortex identification method was employed to identify various vortical structures in the flow. The secondary flow structures in the planar compliant model with dilatation of 0.61%-3.23% under pulsatile flow rate were compared with the rigid vessel model results, and it was found that local vessel compliance has a negligible effect on secondary flow morphology. The secondary flow structures were found to be more sensitive to out of plane curvature (torsion) than to vessel compliance. Torsion distorts the symmetry of secondary flow and results in more complex vortical structures in both steady and pulsatile flows. In high Re number steady flow with torsion, a single dominant vortical structure can be detected at the middle of the 90° cross section. In pulsatile flow with torsion, the split-Dean and Lyne-type vortices with same rotation direction originating from opposite sides of the cross section tend to merge together. supported by GW Center for Biomimetics and Bioinspired Engineering.

An intriguing design concept to enhance the pulsatile fatigue life of self-expanding stents.

Science.gov (United States)

Hsiao, Hao-Ming; Yin, Ming-Ting

2014-02-01

Intravascular stenting has emerged as the primary treatment for vascular diseases and has received great attention from the medical community since its introduction two decades ago. The endovascular self-expanding stent is used to treat peripheral artery diseases; however, once implanted, these stents suffer from various cyclic motions caused by pulsatile blood pressure and daily activities. Due to this challenging environment, fatigue performance has become a critical issue for stent design. In this paper, a simple yet intriguing concept of stent design aimed at enhancing pulsatile fatigue life is investigated. The concept of this design is to shift the highly concentrated stresses/strains away from the crown and re-distribute them along the stress-free bar arm by tapering its strut width. Finite element models were developed to evaluate the mechanical integrity and pulsatile fatigue resistance of the stent to various loading conditions. Results show that the fatigue safety factor jumped to 2.5-3.0 times that of the standard stent with constant strut width. This is astonishing considering that the stent profile and scaffolding were not compromised. The findings of this paper provide an excellent approach to the optimization of future stent design to greatly improve stent fatigue performance.

Functional hypothalamic amenorrhea and its influence on women’s health

OpenAIRE

Meczekalski, B.; Katulski, K.; Czyzyk, A.; Podfigurna-Stopa, A.; Maciejewska-Jeske, M.

2014-01-01

Introduction Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea. There are three types of FHA: weight loss-related, stress-related, and exercise-related amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). The final consequences are complex hormonal changes manifested by profound hypoes...

Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

Science.gov (United States)

Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

2017-12-01

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

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Lund Eiliv

2009-07-01

Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

International Nuclear Information System (INIS)

Canzian, Federico; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A; Hankinson, Susan E; Hoover, Robert; Hunter, David J; Isaacs, Claudine; Kaaks, Rudolf; Lenner, Per; Lund, Eiliv; Overvad, Kim; Palli, Domenico; Pearce, Celeste Leigh; Quiros, Jose R; Riboli, Elio; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Cox, David G; Trichopoulos, Dimitrios; Gils, Carla H van; Ziegler, Regina G; Henderson, Katherine D; Henderson, Brian E; Berg, Christine; Bingham, Sheila; Boeing, Heiner; Buring, Julie

2009-01-01

Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians

Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis.

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Bertelloni, Silvano; Massart, Francesco; Miccoli, Mario; Baroncelli, Giampiero I

2017-06-01

Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (-0.559 SDS (95%CI -1.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (-0.557 SDS (95%CI -0.736 to -0.419); P adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty.

Antibodies against gonadotropin-releasing hormone (GnRH) in patients with diabetes mellitus is associated with lower body weight and autonomic neuropathy.

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Berntorp, Kerstin; Frid, Anders; Alm, Ragnar; Fredrikson, Gunilla Nordin; Sjöberg, Klas; Ohlsson, Bodil

2013-08-17

Esophageal dysmotility and gastroparesis are common secondary complications in patients with diabetes mellitus. Patients with dysmotility express antibodies against gonadotropin-releasing hormone (GnRH) in serum. The aim of the present study was to scrutinize patients with diabetes mellitus with regard to the presence of GnRH antibodies, and to examine associations between antibodies and clinical findings. Thirty-nine consecutive patients with diabetes mellitus were included in the study after clinical examination and examination by esophageal manometry and gastric emptying scintigraphy. Serum was analyzed for the presence of antibodies against GnRH using an ELISA, and values are expressed as relative units (RU). Two age- and gender-matched healthy subjects per each patient served as controls. The prevalence of IgM GnRH antibodies in patients was 33% compared to 14% in controls (p = 0.027), with a higher antibody titer; 1.2 (0.6-5.0) and 0.2 (0.1-0.3) RU, respectively (p = 0.000). The expression of IgG antibodies was 15% in patients and none in controls (p = 0.000). Lower body mass index was associated with the presence of IgM antibodies (OR = 0.835, 95% CI = 0.699-0.998), and autonomic neuropathy with the presence IgG antibodies (OR = 9.000, 95% CI = 1.327-61.025). Esophageal dysmotility (69%) or gastroparesis (18%) were not associated with the presence of IgM antibodies (OR = 0.589, 95% CI = 0.143-2.424 and OR = 3.407, 95% CI = 0.633-18.350, respectively). Neither was esophageal dysmotility associated with IgG antibodies (OR = 2.500, 95% CI = 0.259-24.096). Antibodies against GnRH are more common in patients with diabetes mellitus compared with healthy controls. IgM antibodies are associated with lower body mass index and IgG antibodies are associated with autonomic neuropathy.

Biphasic action of cyclic adenosine 3',5'- monophosphate in gonadotropin-releasing hormone (GnRH) analog-stimulated hormone release from GH3 cells stably transfected with GnRH receptor complementary deoxyribonucleic acid.

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Stanislaus, D; Arora, V; Awara, W M; Conn, P M

1996-03-01

GH3 cells are a PRL-secreting adenoma cell line derived from pituitary lactotropes. These cells have been stably transfected with rat GnRH receptor complementary DNA to produce four cell lines: GGH(3)1', GGH(3)2', GGH(3)6', and GGH(3)12'. In response to either GnRH or Buserelin (a metabolically stable GnRH agonist), these cell lines synthesize PRL in a cAMP-dependent manner. Only GGH(3)6' cells desensitize in response to persistent treatment with 10(-7) g/ml Buserelin. GGH(3)1', GGH(3)2', and GGH(3)12' cells, however, can be made refractory to Buserelin stimulation by raising cAMP levels either by the addition of (Bu)2cAMP to the medium or by treatment with cholera toxin. In GGH(3) cells, low levels of cAMP fulfill the requirements for a second messenger, whereas higher levels appear to mediate the development of desensitization. The observation that in GGH(3)6' cells, cAMP production persists after the onset of desensitization is consistent with the view that the mechanism responsible for desensitization is distal to the production of cAMP. Moreover, the absence of any significant difference in the amount of cAMP produced per cell in GGH(3)2', GGH(3)6', or GGH(3)12' cells suggests that elevated cAMP production per cell does not explain the development of desensitization in GGH(3)6' cells. We suggest that Buserelin-stimulated PRL synthesis in GGH(3)6' cells is mediated by a different cAMP-dependent protein kinase pool(s) than that in nondesensitizing GGH(3) cells. Such a protein kinase A pool(s) may be more susceptible to degradation via cAMP-mediated mechanisms than the protein kinase pools mediating the Buserelin response in nondesensitizing GGH(3) cells. A similar mechanism has been reported in other systems.

Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

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Ferrandina, Gabriella; Amadio, Giulia; Marcellusi, Andrea; Azzolini, Elena; Puggina, Anna; Pastorino, Roberta; Ricciardi, Walter; Scambia, Giovanni

2017-11-01

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

Comparison of microdose GnRH agonist protocol with GnRH antagonist / letrazole protocol in patients with poor ovarian response

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Yiğit Çakıroğlu

2013-09-01

Full Text Available Objective: To compare microdose GnRH agonist (MDL protocol with GnRH antagonist/letrazole (AL protocol in patients with poor ovarian response. Design: Randomised clinical trial. Setting: Kocaeli University Assisted Reproductive Centre Interventions: POR was diagnosed according to ESHRE Bologna criteria in case of presence of 2 out of 3 criteria. In the MDL group (n=27, 40µg/0.2 cc subcutaneous leuprolid acetate was given two times a day starting on the first day of menstrual cycle. On the second day of the cycle, gonadotrophin stimulation was started at 450-600 IU and/or 150 IU human menopausal gonadotrophin (hMG along with leuprolid. In the AL group (n=28, 5 mg letrazole was given for 5 days starting on the second day of the spontaneous cycle and after the 5th day of the cycle, 450-600 IU and/or 150 IU hMG was given. Main Outcome Measures: To compare the outcomes of MDL protocol with AL protocol in patients with poor ovarian response. Results: Stimulation days, total gonadotrophin dose (IU, peak E2 (pg/ml levels, and endometrial thickness were found to be statistically significantly lower in the AL group. While no cases of cycle cancellation was detected in the MDL group, statistically significantly higher rates of cycle cancellation (%35.7, p<0.001 was detected in the AL group. No statistically significant differences were detected in total oocyte numbers (3.7±2.9 vs 2.7±2.2, number of transferred embryos (1.4±0.5 vs 1.4±1.9, pregnancy rates (3/27 (%11.1 vs 2/28 (%7.1 and implantation rates (3/36 (%8.3 vs 2/22 (%9.1 in between the groups. Comment: Although AL protocol is not superior to MDL protocol in poor ovarian response patients, it may be used as an alternative protocol.

The terminal nerve plays a prominent role in GnRH-1 neuronal migration independent from proper olfactory and vomeronasal connections to the olfactory bulbs

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Ed Zandro M. Taroc

2017-10-01

Yoshihara et al., 2005. Our data prove that correct development of the OBs and axonal connection of the olfactory/vomeronasal sensory neurons to the forebrain are not required for GnRH-1 ns migration, and suggest that the terminal nerve, which forms the GnRH-1 migratory scaffold, follows different guidance cues and differs in gene expression from olfactory/vomeronasal sensory neurons.

The effect of GnRH or oestradiol injected at pro-oestrus on luteal function and follicular dynamics of the subsequent oestrous cycle in non-lactating cycling Holstein cows

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B.V.E. Segwagwe

2006-09-01

Full Text Available Oestrous synchronization involves synchronization of ovarian follicular turnover, new wave emergence, and finally induction of ovulation. The final step can be synchronized by the parenteral administration of either GnRH or oestradiol benzoate. This study investigated corpus luteum and follicular emergence after ovulation had been induced by the administration of either GnRH or oestradiol benzoate. The injection of oestradiol benzoate may have delayed the emergence of the first follicular wave subsequent to the induced ovulation; administration of oestradiol benzoate or GnRH lowered the progesterone rise so that the maximum dioestrous concentration of progesterone on Day 9 was lower when cows were treated during pro-oestrus compared to the spontaneously ovulating controls. One implication of findings from the present study is that induction of ovulation with either oestradiol benzoate or GnRH, administered 24 or 36 h after withdrawal of the CIDR device, respectively, may lower fertility. Future studies must identify the timing of administration relative to the time of CIDR device withdrawal and the optimum concentration of oestradiol benzoate or GnRH that would not have untoward effects on the development of the corpus lutea, particularly within the first week of dioestrus.

Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

NARCIS (Netherlands)

Heetla, H. W.; Staal, M. J.; van Laar, T.

Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

Neuroanatomical Alterations in Patients with Early Stage of Unilateral Pulsatile Tinnitus: A Voxel-Based Morphometry Study

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Yawen Liu

2018-01-01

Full Text Available During the past several years, the rapid development of neuroimaging techniques has contributed greatly in the noninvasive imaging studies of tinnitus. The aim of the present study was to explore the brain anatomical alterations in patients with right-sided unilateral pulsatile tinnitus (PT in the early stage of PT symptom using voxel-based morphometry (VBM analysis. Twenty-four patients with right-sided pulsatile tinnitus and 24 age- and gender-matched normal controls were recruited to this study. Structural image data preprocessing was performed using VBM8 toolbox. Tinnitus Handicap Inventory (THI score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Two-sample t-test and Pearson’s correlation analysis were used in statistical analysis. Patients with unilateral pulsatile tinnitus had significantly increased gray matter (GM volume in bilateral superior temporal gyrus compared with the normal controls. However, the left cerebellum posterior lobe, left frontal superior orbital lobe (gyrus rectus, right middle occipital gyrus (MOG, and bilateral putamen showed significantly decreased brain volumes. This was the first study which demonstrated the features of neuroanatomical changes in patients with unilateral PT during their early stages of the symptom.

INFLUENCE OF PULSATILE FLOW ON THE BEHAVIOR OF HUMAN FIBROBLASTS ADHERED TO GLASS

NARCIS (Netherlands)

VANKOOTEN, TG; SCHAKENRAAD, JM; VANDERMEI, HC; BUSSCHER, HJ

1993-01-01

In the human body, cells contacting biomaterials surfaces are frequently exposed to pulsatile shear stresses, e.g. blood vessel prostheses. Most studies involving shear, however, try to achieve a steady, pulse-free shear stress in studying cell-biomaterial interactions. In this study, human

Comparative analysis of the pituitary and ovarian GnRH systems in the leopard gecko: signaling crosstalk between multiple receptor subtypes in ovarian follicles.

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Ikemoto, Tadahiro; Park, Min Kyun

2007-02-01

GnRH regulates reproductive functions through interaction with its pituitary receptor in vertebrates. The present study demonstrated that the leopard gecko possessed two and three genes for GnRH ligands and receptors, respectively, though one of the three receptor subtypes had long been thought not to exist in reptiles. Each receptor subtype showed a distinct pharmacology. All types of ligands and receptors showed different expression patterns, and were widely expressed both inside and outside the brain. This report also shows a comparison of the pituitary and ovarian GnRH systems in the leopard gecko during and after the egg-laying season. All three receptor subtypes were expressed in both the whole pituitary and ovary; however, only one receptor subtype could be detected in the anterior pituitary gland. In situ hybridization showed spatial expression patterns of ovarian receptors, and suggested co-expression of multiple receptor subtypes in granulosa cells of larger follicles. Co-transfection of receptor subtypes showed a distinct pharmacology in COS-7 cells compared with those of single transfections. These results suggest that distinct signaling mechanisms are involved in the pituitary and ovarian GnRH systems. Seasonal and developmental variations in receptor expression in the anterior pituitary gland and ovarian follicles may contribute to the seasonal breeding of this animal.

Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support

DEFF Research Database (Denmark)

Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P

2013-01-01

Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?......Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?...

Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion.

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Yang, Ying; Zhou, Li-bin; Liu, Shang-quan; Tang, Jing-feng; Li, Feng-yin; Li, Rong-ying; Song, Huai-dong; Chen, Ming-dao

2005-08-01

To investigate the expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in the control of GnRH secretion. Receptors of bombesin3, cholecystokinin (CCK)-A, CCK-B, glucagon-like peptide (GLP)1, melanin-concentrating hormone (MCH)1, orexin1, orexin2, neuromedin-B, neuropeptide Y (NPY)1 and NPY5, neurotensin (NT)1, NT2, NT3, and leptin receptor long form mRNA in GT1-7 cells were detected by reversed transcriptase-polymerase chain reaction. GT1-7 cells were treated with leptin, orexin A and orexin B at a cohort of concentrations for different lengths of time, and GnRH in medium was determined by radioimmunoassay (RIA). Receptors of bombesin 3, CCK-B, GLP1, MCH1, orexin1, neuromedin-B, NPY1, NPY5, NT1, NT3, and leptin receptor long form mRNA were expressed in GT1-7 cells, of which, receptors of GLP1, neuromedin-B, NPY1, and NT3 were highly expressed. No amplified fragments of orexin2, NT2, and CCK-A receptor cDNA were generated with GT1-7 RNA, indicating that the GT1-7 cells did not express mRNA of them. Leptin induced a significant stimulation of GnRH release, the results being most significant at 0.1 nmol/L for 15 min. In contrast to other studies in hypothalamic explants, neither orexin A nor orexin B affected basal GnRH secretion over a wide range of concentrations ranging from 1 nmol/L to 500 nmol/Lat 15, 30, and 60 min. Feeding and reproductive function are closely linked. Many orexigenic and anorexigenic signals may control feeding behavior as well as alter GnRH secretion through their receptors on GnRH neurons.

Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

International Nuclear Information System (INIS)

Malik, Ritu; Misra, Amit; Tondwal, Shailesh; Venkatesh, K S

2008-01-01

Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

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Malik, Ritu; Tondwal, Shailesh; Venkatesh, K. S.; Misra, Amit

2008-10-01

Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

Characterization and differential expression of three GnRH forms during reproductive development in cultured turbot Schophthalmus maximus

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Zhao, Chunyan; Xu, Shihong; Feng, Chengcheng; Liu, Yifan; Yang, Yang; Wang, Yanfeng; Xiao, Yongshuang; Song, Zongcheng; Liu, Qinghua; Li, Jun

2017-10-01

Turbots (Schophthalmus maximus), one of the most important economic marine flatfish species, fail to undergo final spawning and spermiation naturally under artificial farming conditions. In vertebrates, reproduction is regulated by the brain-pituitary-gonadal axis (BPG-axis), and gonadotropin releasing hormone (GnRH) is one of its key components. Therefore, to better understand the physiology of reproduction in the turbot, three of the genes encoding GnRH subtypes—sbGnRH, cGnRH-II and sGnRH—were cloned and sequenced by isolating the cDNA sequences. The localizations and patterns of expression of their mRNAs were also evaluated during seasonal gonadal development. All three mRNAs were expressed abundantly in the brain; sbGnRH and sGnRH mRNAs were also detected in the gonads and pituitary gland, and sbGnRH expression was much higher than that of sGnRH, indicating the critical role of sbGnRH in regulating the BPG-axis. Moreover, the brain expression patterns of sbGnRH and sGnRH mRNAs showed an increased trend during gonadal development, peaking in mature stages. This indicated the direct regulation of gonadal development by the GnRH system. In addition, cGnRH-II mRNA expression showed no significant variations, suggesting that cGnRH-II is not critically involved in the control of reproduction. Further, the mRNA abundances of the three GnRH forms in the breeding season were significantly higher than those in immature and post-breeding stages in all analyzed brain areas. Therefore, we propose that sbGnRH is the most important hormone for the regulation of reproduction in turbot via the BPG-axis. These results will help in better understanding the reproductive endocrine mechanisms of turbots and lay the groundwork for additional studies aimed at comparing the reproductive physiology of wild individuals with those raised under artificial conditions.

Feasibility Study of Ex Ovo Chick Chorioallantoic Artery Model for Investigating Pulsatile Variation of Arterial Geometry.

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Kweon-Ho Nam

Full Text Available Despite considerable research efforts on the relationship between arterial geometry and cardiovascular pathology, information is lacking on the pulsatile geometrical variation caused by arterial distensibility and cardiomotility because of the lack of suitable in vivo experimental models and the methodological difficulties in examining the arterial dynamics. We aimed to investigate the feasibility of using a chick embryo system as an experimental model for basic research on the pulsatile variation of arterial geometry. Optical microscope video images of various arterial shapes in chick chorioallantoic circulation were recorded from different locations and different embryo samples. The high optical transparency of the chorioallantoic membrane (CAM allowed clear observation of tiny vessels and their movements. Systolic and diastolic changes in arterial geometry were visualized by detecting the wall boundaries from binary images. Several to hundreds of microns of wall displacement variations were recognized during a pulsatile cycle. The spatial maps of the wall motion harmonics and magnitude ratio of harmonic components were obtained by analyzing the temporal brightness variation at each pixel in sequential grayscale images using spectral analysis techniques. The local variations in the spectral characteristics of the arterial wall motion were reflected well in the analysis results. In addition, mapping the phase angle of the fundamental frequency identified the regional variations in the wall motion directivity and phase shift. Regional variations in wall motion phase angle and fundamental-to-second harmonic ratio were remarkable near the bifurcation area. In summary, wall motion in various arterial geometry including straight, curved and bifurcated shapes was well observed in the CAM artery model, and their local and cyclic variations could be characterized by Fourier and wavelet transforms of the acquired video images. The CAM artery model with

Studies on the relationship between thyroid hormones, ovarian hormones, GnRH and reproductive performance of egyptian buffaloes

International Nuclear Information System (INIS)

Farghaly, H.A.M.

1992-01-01

this study was carried out in the experimental farm of animal production department, faculty of agriculture, cairo university. hormonal analysis were performed in the laboratories of animal physiology unit, radiobiology department, nuclear research center, atomic energy authority (radiobiol. Dept., NRC, AEA). The aim of the study was to investigate the following : 1- post-partum reproductive activity of egyptian buffaloes and the factors affecting the resumption of ovarian activity after calving , with particular reference to the patterns of thyroid hormones (T 4 and T 3 ) and progesterone hormone.2- the effectiveness of using GnRH treatment on inducing ovarian activity after calving. 3- the effect of goitrogen administration (thiouracil) on ovarian activity during post-partum and on the response of buffaloes to GnRH treatment and their reproductive patterns

Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude

NARCIS (Netherlands)

Romijn, J. A.; Adriaanse, R.; Brabant, G.; Prank, K.; Endert, E.; Wiersinga, W. M.

1990-01-01

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

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Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells

International Nuclear Information System (INIS)

Yang Chiming; Frei, Hanspeter; Burt, Helen M.; Rossi, Fabio

2009-01-01

Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

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Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

2017-09-01

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing

Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist protocol in poor responders undergoing IVF/ICSI: An RCT

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Robab Davar

2018-04-01

Full Text Available Background: Over the years, many article on different aspects of pathogenesis and management of poor ovarian responders have been published but there is no clear guideline for treating themyet. Objective: This study was designated to compare the effectiveness of a delayed start protocol with gonadotropin-releasing hormone (GnRH antagonist and microdose flare-up GnRH agonist protocol in poor ovarian responders. Materials and Methods: This randomized clinical trial consisted of 100 poor ovarian responder women in assisted reproductive technologies cycles. They were divided randomly in delayed-start antagonist protocol (with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation and microdose flare-up GnRH agonist protocol. The main outcome was clinical pregnancy rate and second outcome was the number of retrieved oocytes, mature oocytes, 2PN number, fertilization rate, and implantation rate. Results: Fertilization rate, clinical pregnancy rate, and ongoing pregnancy rates were not significantly different between the two studied protocols. Number of retrieved oocytes (5.10±3.41 vs. 3.08±2.51 with p=0.002, mature oocytes (4.32±2.69 vs. 2.34±1.80 with p=0.003, number of 2PN (3.94±1.80 vs. 2.20±1.01 with p=0.001 and implantation rate (19.40% vs. 10.30% with p=0.022 were significantly higher in delayed antagonist group. Conclusion: The delayed-start protocol can improve ovarian response in poor responders by stimulating and synchronizing follicle development

EFFECT OF POST-MATING GNRH TREATMET ON SERUM PROGESTERONE, LUTEINIZING HORMONE LEVELS, DURATION OF ESTROUS CYCLE AND PREGNANCY RATES IN COWS

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H. YILDIZ, E. KAYGUSUZOĞLU, M. KAYA1 AND M. ÇENESIZ1

2009-07-01

Full Text Available Pregnancy rate, estrous cycle lenght, serum progesterone and luteinizing hormone (LH concentrations were determined in gonadotropin releasing hormone (GnRH; 10.5 μg synthetic gonadotrophin releasing hormone agonist, receptal administered cows on day 12 post-mating (n=9 compared to control cows (n=8. Their oestrous cycles were synchronised by intramuscular administration of prostaglandin F2 alpha (its analog, cloprostenol twice at 11 days interval. Estrous exhibited cows were mated naturally. Blood samples were collected every two days from all animals. Serum progesterone and LH concentrations were measured by ELISA method. GnRH administration significantly increased serum LH concentration which reached peak levels 2-3 h after treatment. However, serum progesterone concentration was not affected. There were no differences in mean progesterone concentrations on days 12 to 24 post-mating between GnRH administrated and control pregnant cows. However, in non pregnant animals, progesterone concentrations on days 16 in the treated group were lower than control group (P<0.01. Pregnancy diagnosis in animals made by B-mode ultrasonography between the 30th and 35th day showed that 77.7% of treated cows were pregnant compared to 50% in control group. Duration of the estrous cycle in the non-pregnant animals was not affected by the treatment (control, 21.3 ± 0.8 days; treated, 22.5 ± 0.5 days. In conclusion, this study supports the use of GnRH on day 12 post-mating as a method for enhancing pregnancy rates in lactating dairy cattle.

Effects of single dose GnRH agonist as luteal support on pregnancy outcome in frozen-thawed embryo transfer cycles: an RCT

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Robab Davar

2015-08-01

Full Text Available Background: There is no doubt that luteal phase support is essential to enhance the reproductive outcome in IVF cycles. In addition to progesterone and human chorionic gonadotropin, several studies have described GnRH agonists as luteal phase support to improve implantation rate, pregnancy rate and live birth rate, whereas other studies showed dissimilar conclusions. All of these studies have been done in fresh IVF cycles. Objective: To determine whether an additional GnRH agonist administered at the time of implantation for luteal phase support in frozen-thawed embryo transfer (FET improves the embryo developmental potential. Materials and Methods: This is a prospective controlled trial study in 200 FET cycles, patients were randomized on the day of embryo transfer into group 1 (n=100 to whom a single dose of GnRH agonist (0.1 mg triptorelin was administered three days after transfer and group 2 (n=100, who did not receive agonist. Both groups received daily vaginal progesterone suppositories plus estradiol valerate 6 mg daily. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were implantation rate, chemical, ongoing pregnancy rate and abortion rate. Results: A total of 200 FET cycles were analyzed. Demographic data and embryo quality were comparable between two groups. No statistically significant difference in clinical and ongoing pregnancy rates was observed between the two groups (26% versus 21%, p=0.40 and 21% versus 17%, p=0.37, respectively. Conclusion: Administration of a subcutaneous GnRH agonist at the time of implantation does not increase clinical or ongoing pregnancy.

Experimental study on quantitative evaluation of slow pulsatile flow of CSF with cine MRI

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Matsuda, Masao

1991-01-01

The present study was designed to evaluate the slow pulsatile flow of cerebrospinal fluid (CSF) quantitatively with cine MRI in phantom experiment for the clinical application. The flow phantom was constructed from a plastic tube with a narrow channel to represent the central aqueduct. The phantom was filled with water to represent the CSF. The second tube filled with stationary water was positioned beside the flow phantom and acted as a control for no-flow signal strength. The ratio of signal intensity in regions of interest for the flow phantom and the control was measured. Not only the actual velocity curve of the flowing water through the phantom but also the temporal profile of signal intensity showed two main peaks with other small peaks in one cycle. This suggested a close relationship between signal intensity of cine MRI and flow velocity. A significant correlation between the signal intensity ratio and the velocity was obtained on cine MRI pulse sequences. Cine MRI was thus found to have the ability to give quantitative information about slow pulsatile flow. The most suitable pulse sequence was fast imaging with steady state free precession pulse sequence at the flip angle between 50 and 90 degrees. This preliminary study suggests that the slow pulsatile flow of CSF passing along the aqueduct can be visualized and measured. Thus, the sequence proposed has a potential for the investigation of normal and disturbed CSF circulation and the mapping of the flow pattern in different pathological conditions. (N.K.)

Endocrine Aspects of 4H Leukodystrophy: A Case Report and Review of the Literature

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Emma Billington

2015-01-01

Full Text Available Introduction. 4H leukodystrophy is an autosomal recessive RNA polymerase III-related leukodystrophy, characterized by hypomyelination, with or without hypodontia (or other dental abnormalities and hypogonadotropic hypogonadism. Case Presentation. We describe a 28-year-old female who presented with primary amenorrhea at the age of 19. She had a history of very mild neurological and dental abnormalities. She was found to have hypogonadotropic hypogonadism, and magnetic resonance imaging of the brain showed hypomyelination. The diagnosis of 4H leukodystrophy was made. She was subsequently found to have mutations in the POLR3B gene, which encodes the second largest subunit of RNA polymerase III. She wished to become pregnant and failed to respond to pulsatile GnRH but achieved normal follicular growth and ovulation with subcutaneous gonadotropin therapy. Discussion. Patients with 4H leukodystrophy may initially present with hypogonadotropic hypogonadism, particularly if neurological and dental manifestations are subtle. Making the diagnosis has important implications for prognosis and management. Progressive neurologic deterioration is expected, and progressive endocrine dysfunction may occur. Patients with 4H leukodystrophy should be counseled about disease progression and about this disease’s autosomal recessive inheritance pattern. In those who wish to conceive, ovulation induction may be achieved with subcutaneous gonadotropin therapy, but pulsatile GnRH does not appear to be effective.

Treatment of cellulite with a bipolar radiofrequency, infrared heat, and pulsatile suction device: a pilot study.

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Wanitphakdeedecha, Rungsima; Manuskiatti, Woraphong

2006-12-01

Very few therapeutic options have proven effective in the treatment of cellulite. To evaluate the effectiveness and adverse effects of a bipolar radiofrequency (RF), infrared (IR) heat and pulsatile suction device for the treatment of cellulite. Twelve subjects were treated with the RF-light-based device. All subjects were treated twice weekly for a total number of eight to nine treatments. Subjects were evaluated using standardized photographs, and measurements of body weight and circumference of treatment sites at baseline, immediately after the last treatment, and four weeks and one year after the last treatment. Clinical improvement scores of comparable photographs using a quartile grading scale (0 = 75% improvement) were judged independently by two non-treating dermatologists after the series of treatment. The average body weights at baseline, immediately after the last treatment, and four weeks and one year after the complete treatment were 56.30, 56.05, 56.23, and 56.53 kg, respectively. The average circumferential reductions of the abdomen and thigh at the last treatment visit were 5.17 +/- 1.04 cm (6.32%+/- 1.82%) and 3.50 +/- 2.16 cm (6.23 +/- 3.58%), respectively. At four weeks after the last treatment, the average circumferential reductions of the abdomen and thigh were sustained at 3.17 +/- 2.75 cm (4.04%+/- 3.69%) and 3.50 +/- 2.04 cm (6.26%+/- 3.52%), respectively. At one year follow-up visit, the average circumferential reductions of the abdomen and thigh were maintained at 3.83 +/- 0.76 cm (4.64%+/- 1.15%) and 3.13 +/- 3.54 (5.50%+/- 6.12%), respectively. Average clinical improvement scores of the abdomen and thigh after the series of treatments were 0.75 (corresponding to approximately 25% improvement), and 1.75 (corresponding to approximately 50% improvement), respectively. A bipolar RF, IR heat and pulsatile suction device provides a beneficial effect on reduction of abdomen and thigh circumference, and smoothening of the cellulite.

Real time monitoring of pulsatile change in hemoglobin concentrations of cerebral tissue by a portable tissue oximeter with a 10-Hz sampling rate

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Shiga, Toshikazu; Chihara, Eiichi; Tanabe, Kazuhisa; Tanaka, Yoshifumi; Yamamoto, Katsuyuki

1998-01-01

A portable CW tissue oximeter of a 10-Hz sampling rate was developed for examination of pulsatile components of the output signals as a mean of checking the signal reliability during long-term monitoring. Feasible studies were performed on a healthy subject. Changes in Hb and HbO2 signals of cerebral tissue were continuously measured by placing a photoprobe on the forehead during 6-hour sleep. Pulsatile changes in Hb and HbO2 were steadily observed over a whole period of the recording. The phase relation of pulsation in Hb and HbO2 was almost inverse. Not only information for reliable monitoring but also physiological parameters with respect to cerebral circulation and metabolism could be obtained by measuring the pulsatile components.

THE USE OF GnRH ANTAGONISTS IN OVARIAN STIMULATION FOR INTRAUTERINE INSEMINATION

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Mete Işıkoğlu

2013-12-01

Full Text Available The first paper entitled intrauterine insemination (IUI was published in 1962. By time, several methods involving the technique and the ovulation induction schedules have evolved in order to improve the success rates. Although gonadotrophin releasing hormone antagonists (GnRHa is a crucial part of assisted reproductive treatments now, concerns also arouse regarding the need for the use of it in IUI cycles. These drugs may be considered in IUI programs basically in order to prevent premature LH surges and related cycle cancellations. Although administration of a GnRH antagonist almost completely abolishes premature luteinization, it does not substantially improve the pregnancy rate. The decision of using GnRH antagonists in IUI cycles should be based primarily on the local cost/benefit analysis of individual centers. It will be prudent to limit the involvement of the antagonists in ovulation induction protocols to: patients who frequently exhibit premature LH discharges and therefore either fail to complete treatment or result in unsuccessful outcome; initiated cycles intented for IUI but converted to ART; if it is not possible for logistic reasons (weekend to perform the insemination or for medical centers in which a gynecologist on call is not available and in order to decrease clinical task burden resulting from strict cycle monitoring such as serial transvaginal sonography and/or frequent urine tests.

Long-Term Durability Test for the Left Ventricular Assist System EVAHEART under the Physiologic Pulsatile Load.

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Kitano, Tomoya; Iwasaki, Kiyotaka

The EVAHEART Left Ventricular Assist System (LVAS) was designed for the long-term support of a patient with severe heart failure. It has an original water lubrication system for seal and bearing and wear on these parts was considered one of its critical failure modes. A durability test focusing on wear was designed herein. We developed a mock loop, which generates a physiologic pulsatile flow and is sufficiently durable for a long-term test. The pulsatile load and the low fluid viscosity enable the creation of a severe condition for the mechanical seal. A total of 18 EVAHEART blood pumps completed 2 years of operation under the pulsatile condition without any failure. It indicated the EVAHEART blood pump had a greater than 90% reliability with a 88% confidence level. The test was continued with six blood pumps and achieved an average of 8.6 years, which was longer than the longest clinical use in Japan. The test result showed that no catastrophic, critical, marginal, or minor failures of the blood pump or their symptoms were observed. The seal performance was maintained after the test. Moreover, the surface roughness did not change, which showed any burn or abnormal wear occurred. The original water lubrication system equipped in EVAHEART LVAS prevent severe wear on the seal and the bearing, and it can be used in the bridge to transplant and destination therapy.

Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

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Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

2016-08-01

Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

Pulsatile spiral blood flow through arterial stenosis.

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Linge, Fabian; Hye, Md Abdul; Paul, Manosh C

2014-11-01

Pulsatile spiral blood flow in a modelled three-dimensional arterial stenosis, with a 75% cross-sectional area reduction, is investigated by using numerical fluid dynamics. Two-equation k-ω model is used for the simulation of the transitional flow with Reynolds numbers 500 and 1000. It is found that the spiral component increases the static pressure in the vessel during the deceleration phase of the flow pulse. In addition, the spiral component reduces the turbulence intensity and wall shear stress found in the post-stenosis region of the vessel in the early stages of the flow pulse. Hence, the findings agree with the results of Stonebridge et al. (2004). In addition, the results of the effects of a spiral component on time-varying flow are presented and discussed along with the relevant pathological issues.

A High Performance Pulsatile Pump for Aortic Flow Experiments in 3-Dimensional Models.

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Chaudhury, Rafeed A; Atlasman, Victor; Pathangey, Girish; Pracht, Nicholas; Adrian, Ronald J; Frakes, David H

2016-06-01

Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies, as well as for planning their surgical repair. In vitro experiments are required to validate the simulations against real world data, and the experiments require a pulsatile flow pump system that can provide physiologic flow conditions characteristic of the aorta. We designed a newly capable piston-based pulsatile flow pump system that can generate high volume flow rates (850 mL/s), replicate physiologic waveforms, and pump high viscosity fluids against large impedances. The system is also compatible with a broad range of fluid types, and is operable in magnetic resonance imaging environments. Performance of the system was validated using image processing-based analysis of piston motion as well as particle image velocimetry. The new system represents a more capable pumping solution for aortic flow experiments than other available designs, and can be manufactured at a relatively low cost.

Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both Pituitary LH and GnRH Receptor Expression

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Jérémy Pasquier

2018-01-01

Full Text Available The European eel (Anguilla anguilla presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. We previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of two Kiss genes. In the present study, we cloned and sequenced Kiss1 and Kiss2 cDNAs from the eel brain. The tissue distributions of Kiss1 and Kiss2 transcripts, as investigated by quantitative real-time PCR, showed that both genes are primarily expressed in the eel brain and pituitary. The two 10-residue long sequences characteristic of kisspeptin, eel Kp1(10 and Kp2(10, as well as two longer sequences, predicted as mature peptides, eel Kp1(15 and Kp2(12, were synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected Chinese hamster ovary cells, we found that the four synthesized eel peptides were able to induce [Ca2+]i responses, indicating their ability to bind mammalian KissR-1 and to activate second messenger pathways. In primary culture of eel pituitary cells, all four peptides were able to specifically and dose-dependently inhibit lhβ expression, without any effect on fshβ, confirming our previous data with heterologous kisspeptins. Furthermore, in this eel in vitro system, all four peptides inhibited the expression of the type 2 GnRH receptor (gnrh-r2. Our data revealed a dual inhibitory effect of homologous kisspeptins on both pituitary lhβ and gnrh-r2 expression in the European eel.

The Effect of Pulsatile Flow on bMSC-Derived Endothelial-Like Cells in a Small-Sized Artificial Vessel Made by 3-Dimensional Bioprinting

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Kang Woog Lee

2018-01-01

Full Text Available Replacement of small-sized vessels is still challenging. This study is aimed at investigating the possibility of small-sized artificial vessels made by 3-dimensional bioprinting and the effect of pulsatile flow on bMSC-derived endothelial-like cells. Cells were harvested from rabbit bone marrow and primary cultured with or without growth factors. Endothelial differentiation was confirmed by the Matrigel tube formation assay, Western blot, and qRT-PCR. In addition, embedment of endothelial-like cells in an artificial vessel was made by 3-dimensional bioprinting, and the pulsatile flow was performed. For pumped and nonpumped groups, qRT-PCR was performed on CD31 and VE-cadherin gene expression. Endothelial-like cells showed increased gene expression of CD31 and VE-cadherin, and tube formation is observed at each week. Endothelial-like cells grow well in a small-sized artificial vessel made by 3-dimensional bioprinting and even express higher endothelial cell markers when they undergo pulsatile flow condition. Moreover, the pulsatile flow condition gives a positive effect for cell observation not only on the sodium alginate hydrogel layer but also on the luminal surface of the artificial vessel wall. We have developed an artificial vessel, which is a mixture of cells and carriers using a 3-dimensional bioprinting method, and applied pulsatile flow using a peristaltic pump, and we also demonstrated cell growth and differentiation into endothelial cells. This study suggests guidelines regarding a small-sized artificial vessel in the field of tissue engineering.

Female-Specific Glucose Sensitivity of GnRH1 Neurons Leads to Sexually Dimorphic Inhibition of Reproduction in Medaka.

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Hasebe, Masaharu; Kanda, Shinji; Oka, Yoshitaka

2016-11-01

Close interaction exists between energy-consuming reproduction and nutritional status. However, there are differences in costs and priority for reproduction among species and even between sexes, which leads to diversification of interactions between reproduction and nutritional status. Despite such diversified interactions among species and sexes, most of the analysis of the nutritional status-dependent regulation of reproduction has been limited to an endothermic vertebrate, mammalian species of either sex. Therefore, the mechanisms underlying the diversified interactions remain elusive. In the present study, we demonstrated the effects of malnutritional status on reproduction at both organismal and cellular levels in an ectothermic vertebrate, a teleost medaka of both sexes. First, we analyzed the effects of malnutrition by fasting on gonadosomatic index, number of spawned/fertilized eggs, and courtship behavior. Fasting strongly suppressed reproduction in females but, surprisingly, not in males. Next, we analyzed the effects of fasting on firing activity of hypothalamic GnRH1 neurons, which form the final common pathway for the control of reproduction. An electrophysiological analysis showed that low glucose, which is induced by fasting, directly suppresses the firing activity of GnRH1 neurons specifically in females through intracellular ATP-sensitive potassium channels and AMP-activated protein kinase pathways. Based on the fact that such suppressions occurred only in females, we conclude that nutritional status-dependent, glucose-sensing in GnRH1 neurons may contribute to the most fitted reproductive regulation for each sex.

Effects of GnRH vaccination in wild and captive African Elephant bulls (Loxodonta africana on reproductive organs and semen quality.

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Imke Lueders

Full Text Available Although the African elephant (Loxodonta africana is classified as endangered by the International Union for Conservation of Nature (IUCN, in some isolated habitats in southern Africa, contraception is of major interest due to local overpopulation. GnRH vaccination has been promoted as a non-invasive contraceptive measure for population management of overabundant wildlife. We tested the efficacy of this treatment for fertility control in elephant bulls.In total, 17 male African elephants that were treated with a GnRH vaccine were examined in two groups. In the prospective study group 1 (n = 11 bulls, ages: 8-36 years, semen quality, the testes, seminal vesicles, ampullae and prostate, which were all measured by means of transrectal ultrasound, and faecal androgen metabolite concentrations were monitored over a three-year period. Each bull in the prospective study received 5 ml of Improvac® (1000 μg GnRH conjugate intramuscularly after the first examination, followed by a booster six weeks later and thereafter every 5-7 months. In a retrospective study group (group 2, n = 6, ages: 19-33 years, one examination was performed on bulls which had been treated with GnRH vaccine for 5-11 years.In all bulls of group 1, testicular and accessory sex gland sizes decreased significantly after the third vaccination. In six males examined prior to vaccination and again after more than five vaccinations, the testis size was reduced by 57.5%. Mean testicular height and length decreased from 13.3 ± 2.6 cm x 15.2 ± 2.8 cm at the beginning to 7.6 ± 2.1 cm x 10.2 ± 1.8 cm at the end of the study. Post pubertal bulls (>9 years, n = 6 examined prior to vaccination produced ejaculates with viable spermatozoa (volume: 8-175 ml, sperm concentration: 410-4000x106/ml, total motility: 0-90%, while after 5-8 injections, only 50% of these bulls produced ejaculates with a small number of immotile spermatozoa. The ejaculates of group 2 bulls (vaccinated >8 times were

FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat

NARCIS (Netherlands)

Schuiling, GA; Valkhof, N; Koiter, TR

The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin(R); 10 IU/injection) lowered the spontaneous pre-ovulatory

Partial thickness autologus calvarial bone orbitocranioplasty for a sphenorbital encephalocele presenting as pulsatile exophthalmos

OpenAIRE

Trivedi, Adarsh; Garg, Amrish Kumar; Hiran, Subodh

2015-01-01

Basal encephalocele accounts only 1.5% of all encephaloceles. But Sphenorbital encephalocele is the rarest cause of herniation of brain into orbit leading to pulsatile exphothalmos. Authors presenting a case of sphenorbital encephalocele in a 16 yrs old girl successsfully managed by orbitcranioplasty by partilal thickness autologus calvarial bone graft.

Secondary flow vortical structures in a 180∘ elastic curved vessel with torsion under steady and pulsatile inflow conditions

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Najjari, Mohammad Reza; Plesniak, Michael W.

2018-01-01

Secondary flow structures in a 180∘ curved pipe model of an artery are studied using particle image velocimetry. Both steady and pulsatile inflow conditions are investigated. In planar curved pipes with steady flow, multiple (two, four, six) vortices are detected. For pulsatile flow, various pairs of vortices, i.e., Dean, deformed-Dean, Lyne-type, and split-Dean, are present in the cross section of the pipe at 90∘ into the bend. The effects of nonplanar curvature (torsion) and vessel dilatation on these vortical structures are studied. Torsion distorts the symmetric secondary flows (which exist in planar curvatures) and can result in formation of more complex vortical structures. For example, the split-Dean and Lyne-type vortices with same rotation direction originating from opposite sides of the cross section tend to merge together in pulsatile flow. The vortical structures in elastic vessels with dilatation (0.61%-3.23%) are also investigated and the results are compared with rigid model results. It was found that the secondary flow structures in rigid and elastic models are similar, and hence the local compliance of the vessel does not affect the morphology of secondary flow structures.

Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

International Nuclear Information System (INIS)

Schmitz, O.; Arnfred, J.; Hother Nielsen, O.; Beck-Nielsen, H.; Oerskov, H.

1986-01-01

To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45mU/kg · min or in identical amounts in pulses of 1 1 / 2 to 2 1 / 4 min followed by intervals of 10 1 / 2 to 9 3 / 4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7±0.7 vs 6.8±0.9 ml/kg · min, P 3 H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion. (author)

Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders.

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Karimzadeh, Mohammad Ali; Mashayekhy, Mehri; Mohammadian, Farnaz; Moghaddam, Fatemeh Mansoori

2011-05-01

To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

NARCIS (Netherlands)

Oostdijk, W; Rikken, B; Schreuder, S; Otten, Barto; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

1996-01-01

Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were

Aneurysm pulsatility after endovascular exclusion: an experimental study using human aortic aneurysms

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Hussein Amin Orra

2008-01-01

Full Text Available OBJECTIVE: To measure the pulsatility of human aneurysms before and after complete exclusion with an endograft. METHOD: Five aortic aneurysms obtained during necropsy were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. The specimens were contained in a closed chamber filled with saline solution. A vertical tube attached to the chamber was used to measure volume dislocation in each systole. Mural thrombus was kept intact, and the space around the device was filled with human blood. After each experiment, the aneurysm was opened to check for the correct positioning and attachment of the device. RESULTS: The level of the saline column oscillated during pulsation in each case, with respective amplitudes of 17, 16, 13, 7, and 25 cm before the endograft insertion. After the insertion, the amplitudes dropped to 13, 12, 9, 3.5, and 23 cm, respectively. The differences were not significant. During the post-experimental examination, all devices were found to be in position and well attached to the neck and iliacs. No endoleak was detected during perfusion or by visual inspection. CONCLUSION: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak, and should not be interpreted as procedural failure.

GnRH antagonist versus long agonist protocols in IVF

DEFF Research Database (Denmark)

Lambalk, C B; Banga, F R; Huirne, J A

2017-01-01

BACKGROUND: Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist...... was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF...

Role of color Doppler US in the evaluation of uterine leiomyoma treated with gonadotrophin-releasing hormone (GnRH) agonist (Zoladex)

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Kim, Jung Sik; Sohn, Cheol Ho; Lee, Tae Sung [Keimyung University Dongsan Medical Center, Taegu (Korea, Republic of)

1999-03-15

To access the role of color Doppler US in the evaluation of uterine leiomyoma treated with GnRH agonist (Zoladex). Out of 25 patients with uterine leiomyoma treated with Zoladex, nineteen cases of leiomyoma in 18 women who had US examination before and after medication were included in this study. Zoladex was injected subcutaneously three times within three months. Both gray scale and color Doppler US were obtained before and 1-3 months after the medication. The size, volume, location and internal echoes of the leiomyoma were recorded with gray scale US. Changes in the amount of color signal within leiomyomas were recorded. Pulsatility index (PI), resistive index (RI), peak systolic velocity (PSV) of both uterine artery and arteries within leiomyomas were also recorded. The image findings of good response group and poor response group in which the volume reduction of the leiomyoma was above or below 50% respectively were compared with each other. The reduction of the volume of leiomyoma was compared between a group with decrease in the amount of color signals during follow-up US and a group with increase or no change. Mean reduction of the volume of leiomyomas was 52%. Changes in the amount of color signals of the leiomyoma, PI, RI, PSV obtained from the arteries within leiomyomas were not correlated with the change of the volume of leiomyomas. PSV of uterine artery in one month follow-up and PI of two month follow-up were correlated with the changes of the volume of leiomyomas (p<0.05). RI of uterine artery in two month follow-up was useful in prediction of the good response group and the poor response group (p<0.05). The prediction of the volume reduction of leiomyoma following Zoladex medication might be possible by obtaining RI of uterine artery in two month follow-up. Doppler US of the arteries within the leiomyoma was not useful.

Role of color Doppler US in the evaluation of uterine leiomyoma treated with gonadotrophin-releasing hormone (GnRH) agonist (Zoladex)

International Nuclear Information System (INIS)

Kim, Jung Sik; Sohn, Cheol Ho; Lee, Tae Sung

1999-01-01

To access the role of color Doppler US in the evaluation of uterine leiomyoma treated with GnRH agonist (Zoladex). Out of 25 patients with uterine leiomyoma treated with Zoladex, nineteen cases of leiomyoma in 18 women who had US examination before and after medication were included in this study. Zoladex was injected subcutaneously three times within three months. Both gray scale and color Doppler US were obtained before and 1-3 months after the medication. The size, volume, location and internal echoes of the leiomyoma were recorded with gray scale US. Changes in the amount of color signal within leiomyomas were recorded. Pulsatility index (PI), resistive index (RI), peak systolic velocity (PSV) of both uterine artery and arteries within leiomyomas were also recorded. The image findings of good response group and poor response group in which the volume reduction of the leiomyoma was above or below 50% respectively were compared with each other. The reduction of the volume of leiomyoma was compared between a group with decrease in the amount of color signals during follow-up US and a group with increase or no change. Mean reduction of the volume of leiomyomas was 52%. Changes in the amount of color signals of the leiomyoma, PI, RI, PSV obtained from the arteries within leiomyomas were not correlated with the change of the volume of leiomyomas. PSV of uterine artery in one month follow-up and PI of two month follow-up were correlated with the changes of the volume of leiomyomas (p<0.05). RI of uterine artery in two month follow-up was useful in prediction of the good response group and the poor response group (p<0.05). The prediction of the volume reduction of leiomyoma following Zoladex medication might be possible by obtaining RI of uterine artery in two month follow-up. Doppler US of the arteries within the leiomyoma was not useful.

Anti-inflammatory effect with high intensity focused ultrasound-mediated pulsatile delivery of diclofenac.

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Wang, Chih-Yu; Yang, Chih-Hui; Lin, Yung-Sheng; Chen, Chih-Hsin; Huang, Keng-Shiang

2012-02-01

A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of the in vitro study show that an approx. 30% higher drug release rate was obtained by using continuous ultrasound irradiation (9-Watt, 180 min), and an approx. 16% higher drug release rate was obtained by using pulsatile ultrasound irradiation (9-Watt, 60 min) compared to without ultrasound activation. For the in vivo study, the anti-inflammatory test with carrageenan-induced rat's paw edema shows that diclofenac-loaded microcapsules followed by ultrasound irradiation (9-Watt, 60 min) contributed to an 81% inhibition rate, which was significantly higher than diclofenac only (approx. 60% higher). In addition, because of their heat conducting properties, gold nanoparticles encapsulated in the diclofenac-loaded microcapsules resulted in better drug release efficiency, but tended to depress the anti-inflammation effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients.

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Kanadani, Fabio N; Figueiredo, Carlos R; Miranda, Rafaela Morais; Cunha, Patricia Lt; M Kanadani, Tereza Cristina; Dorairaj, Syril

2015-01-01

Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student's t-test. The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19.

Effects of Huang Bai (Phellodendri Cortex and Three Other Herbs on GnRH and GH Levels in GT1–7 and GH3 Cells

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Sun Haeng Lee

2016-01-01

Full Text Available The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1–7 and GH3 cells. The GT1–7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 μg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1–7 and GH3 cells were incubated in DW, estradiol (GT1–7 only, or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1–7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1–7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1–7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary.

Mathematical Modelling of CSF Pulsatile Flow in Aqueduct Cerebri.

Science.gov (United States)

Czosnyka, Zofia; Kim, Dong-Joo; Balédent, Olivier; Schmidt, Eric A; Smielewski, Peter; Czosnyka, Marek

2018-01-01

The phase-contrast MRI technique permits the non-invasive assessment of CSF movements in cerebrospinal fluid cavities of the central nervous system. Of particular interest is pulsatile cerebrospinal fluid (CSF) flow through the aqueduct cerebri. It is allegedly increased in hydrocephalus, having potential diagnostic value, although not all scientific reports contain unequivocally positive conclusions. For the mathematical simulation of CSF flow, we used a computational model of cerebrospinal blood/fluid circulation designed by a former student as his PhD project. With this model, cerebral blood flow and CSF may be simulated in various vessels using a system of non-linear differential equations as time-varying signals. The amplitude of CSF flow seems to be positively related to the amplitude of pulse waveforms of intracranial pressure (ICP) in situations where mean ICP increases, such as during simulated infusion tests and following step increases of resistance to CSF outflow. An additional positive association between the pulse amplitude of ICP and CSF flow can be seen during simulated increases in the amplitude of arterial pulses (without changes in mean arterial pressure, MAP). The opposite effect can be observed during step increases in the resistance of the aqueduct cerebri and with decreasing elasticity of the system, where the CSF flow amplitude and the ICP pulse amplitude are related inversely. Vasodilatation caused by both gradual decreases in MAP and by increases in PaCO2 provokes an elevation in the observed amplitude of pulsatile CSF flow. Preliminary results indicate that the pulsations of CSF flow may carry information about both CSF-circulatory and cerebral vasogenic components. In most cases, the pulsations of CSF flow are positively related to the pulse amplitudes of both arterial pressure and ICP and to a degree of cerebrovascular dilatation.

GnRH-induced Ca2+ signaling patterns and gonadotropin secretion in pituitary gonadotrophs. Functional adaptations to both ordinary and extraordinary physiological demands

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María Luisa eDurán-Pastén

2013-09-01

Full Text Available Pituitary gonadotrophs are a small fraction of the anterior pituitary population, yet they synthesize gonadotropins: luteinizing (LH and follicle stimulating (FSH, essential for gametogenesis and steroidogenesis. LH is secreted via a regulated pathway while FSH release is mostly constitutive and controlled by synthesis. Although gonadotrophs fire action potentials spontaneously, the intracellular Ca2+ rises produced do not influence secretion, which is mainly driven by Gonadotropin Releasing Hormone (GnRH, a decapeptide synthesized in the hypothalamus and released in a pulsatile manner into the hypophyseal portal circulation. GnRH binding to G protein coupled receptors triggers Ca2+ mobilization from InsP3-sensitive intracellular pools, generating the global Ca2+ elevations necessary for secretion. Ca2+ signaling responses to increasing [GnRH] vary in stereotyped fashion from subthreshold to baseline spiking (oscillatory, to biphasic (spike-oscillatory or spike-plateau. This progression varies somewhat in gonadotrophs from different species and biological preparations. Both baseline spiking and biphasic GnRH-induced Ca2+ signals control LH/FSH synthesis and exocytosis. Estradiol and testosterone regulate gonadotropin secretion through feedback mechanisms, while FSH synthesis and release are influenced by activin, inhibin and follistatin. Adaptation to physiological events like the estrous cycle, involves changes in GnRH sensitivity and LH/FSH synthesis: in proestrus, estradiol feedback regulation abruptly changes from negative to positive, causing the pre-ovulatory LH surge. Similarly, when testosterone levels drop after orquiectomy the lack of negative feedback on pituitary and hypothalamus boosts both GnRH and LH secretion, gonadotrophs GnRH sensitivity increases and Ca2+ signaling patterns change. In addition, gonadotrophs proliferate and grow. These plastic changes denote a more vigorous functional adaptation in response to an extraordinary

Electroresponsive polymer-carbon nanotube hydrogel hybrids for pulsatile drug delivery in vivo.

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Servant, Ania; Methven, Laura; Williams, Rhodri P; Kostarelos, Kostas

2013-06-01

Drug release triggered by an external non-invasive stimulus is of great interest for the development of new drug delivery systems. The preparation of an electroresponsive multiwalled carbon nanotube/poly(methylacrylic acid) (MWNT/PMAA)-based hybrid material is reported. The hydrogel hybrids achieve a controlled drug release upon the ON/OFF application of an electric field, giving rise to in vitro and in vivo pulsatile release profiles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lactobacillus rhamnosus accelerates zebrafish backbone calcification and gonadal differentiation through effects on the GnRH and IGF systems.

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Matteo A Avella

Full Text Available Endogenous microbiota play essential roles in the host's immune system, physiology, reproduction and nutrient metabolism. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's development. Thus, we treated zebrafish from birth to sexual maturation (2-months treatment with Lactobacillus rhamnosus, a probiotic species intended for human use. We monitored for the presence of L. rhamnosus during the entire treatment. Zebrafish at 6 days post fertilization (dpf exhibited elevated gene expression levels for Insulin-like growth factors -I and -II, Peroxisome proliferator activated receptors -α and -β, VDR-α and RAR-γ when compared to untreated-10 days old zebrafish. Using a gonadotropin-releasing hormone 3 GFP transgenic zebrafish (GnRH3-GFP, higher GnRH3 expression was found at 6, 8 and 10 dpf upon L. rhamnosus treatment. The same larvae exhibited earlier backbone calcification and gonad maturation. Noteworthy in the gonad development was the presence of first testes differentiation at 3 weeks post fertilization in the treated zebrafish population -which normally occurs at 8 weeks- and a dramatic sex ratio modulation (93% females, 7% males in control vs. 55% females, 45% males in the treated group. We infer that administration of L. rhamnosus stimulated the IGF system, leading to a faster backbone calcification. Moreover we hypothesize a role for administration of L. rhamnosus on GnRH3 modulation during early larval development, which in turn affects gonadal development and sex differentiation. These findings suggest a significant role of the microbiota composition on the host organism development profile and open new perspectives in the study of probiotics usage and application.

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study.

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Faulisi, Sonia; Reschini, Marco; Borroni, Raffaella; Paffoni, Alessio; Busnelli, Andrea; Somigliana, Edgardo

2017-01-01

The routine assessment of day 3 serum progesterone prior to initiation of ovarian hyper-stimulation with the use of GnRH antagonists is under debate. In this study, we evaluated the clinical utility of this policy. Retrospective cohort study of women undergoing in vitro fertilization (IVF) with the use of GnRH antagonists aimed at determining the frequency of cases with progesterone levels exceeding the recommended threshold of 1,660 pg/ml and at evaluating whether this assessment may be predictive of pregnancy. Serum progesterone exceeded the recommended threshold in one case (0.3%, 95% CI 0.01-1.5). The median (interquartile range) basal progesterone in women who did (n = 95) and did not (n = 217) become pregnant were 351 (234-476) and 380 (237-531) pg/ml, respectively (p = 0.28). The 90th percentile of the basal progesterone distribution in women who became pregnant was 660 pg/ml. Cases with serum progesterone exceeding this threshold in successful and unsuccessful cycles were 10 (10%) and 30 (14%), respectively (p = 0.47). The capacity of basal progesterone to predict pregnancy was evaluated using receiver operating characteristic curve (area under the curve = 0.54, 95% CI 0.47-0.61, p = 0.28). No graphically evident threshold emerged. Routine day 3 serum progesterone assessment in IVF cycles with the use of GnRH antagonists is not justified. Further evidence is warranted prior to claiming its systematic use. © 2016 S. Karger AG, Basel.

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

DEFF Research Database (Denmark)

Juul, A; Scheike, Thomas Harder; Nielsen, C T

1995-01-01

Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.

Science.gov (United States)

Bahçeci, Mustafa; Ulug, Ulun; Ben-Shlomo, Izhar; Erden, Halit Firat; Akman, Mehmet Ali

2005-02-01

To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART). A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed. None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively). The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.

Karyometric changes of neurons of hypothalamus and ependyma nuclei of the third cerebral ventricle of sheep following administration of Gn-RH and subsequent irradiation

International Nuclear Information System (INIS)

Stanikova, A.; Arendarcik, J.; Tokos, M.; Balun, J.; Chlebovsky, O.

1983-01-01

A karyometric analysis was used for the study of changes in the cell nucleus volume of the neurons of nucleus paraventricularis, nucleus arcuatus, and the ependyma of the third cerebral ventricle of sheep after the administration of Gn-RH, followed by exposure to X rays. The test animals included 12 ewes in physiological anoestrus and two rams. The trials were conducted in spring. The first group of four ewes and two rams were left as controls; in the ewes of the second group the hypothalamo-hypophysial region was irradiated with 516.5 mC/kg (200 R);in the four ewes of the third group, ovaries were directly irradiated at laparotomy with 64.4 mC/kg (250 R). The ewes of the second and third groups were treated with i.m. administration of 400 μg Gn-RH per head before irradiation. The excisions were collected and processed the tenth day from irradiation. The karyometric analysis was performed at 3000-fold magnification, 200 cells being measured in each sample. Changes in neurosecretory cells were described in the regions of nucleus paraventricularis, nucleus arcuatus and in the ependyma of the third cerebral ventricle. The results of the karyometric analysis of nucleus paraventricularis and nucleus arcuatus suggest that the administration of Gn-RH and irradiation of the hypothalamo-hypophysial region, and direct irradiation of the ovaries stimulated the studied cerebral structures. The changes observed in the ependyma of the third cerebral ventricle after the administration of Gn-RH and subsequent irradiation of the hypothalamo-hypophysial region were insignificant; it was only after direct irradiation of the ovaries that these cells were inhibited indirectly through the feedback mechanism. (author)

Arduino control of a pulsatile flow rig.

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Drost, S; de Kruif, B J; Newport, D

2018-01-01

This note describes the design and testing of a programmable pulsatile flow pump using an Arduino micro-controller. The goal of this work is to build a compact and affordable system that can relatively easily be programmed to generate physiological waveforms. The system described here was designed to be used in an in-vitro set-up for vascular access hemodynamics research, and hence incorporates a gear pump that delivers a mean flow of 900 ml/min in a test flow loop, and a peak flow of 1106 ml/min. After a number of simple identification experiments to assess the dynamic behaviour of the system, a feed-forward control routine was implemented. The resulting system was shown to be able to produce the targeted representative waveform with less than 3.6% error. Finally, we outline how to further increase the accuracy of the system, and how to adapt it to specific user needs. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

The effects of a slow release GnRH agonist implant on male rabbits

DEFF Research Database (Denmark)

Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

2015-01-01

Surgical castration is done in male pet rabbits for reproduction control, to reduce inter-male aggression and to control hyper-sexuality, territory marking and aggression against humans. Alternatives to surgical castration are requested because of a relatively great anaesthetic risk in rabbits....... Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...

GnRH agonist ovulation trigger and hCG-based, progesterone-free luteal support: a proof of concept study

DEFF Research Database (Denmark)

Kol, Shahar; Humaidan, Peter; Itskovitz-Eldor, Joseph

2011-01-01

in normal responder IVF patients. We here present a novel approach for luteal support after a GnRHa trigger. METHODS Normal responder patients who failed at least one previous IVF attempt, during which a conventional hCG trigger was used, were consecutively enrolled in the study. A GnRH antagonist...

Computational fluid dynamics analysis and PIV validation of a bionic vortex flow pulsatile LVAD.

Science.gov (United States)

Xu, Liang; Yang, Ming; Ye, Lin; Dong, Zhaopeng

2015-01-01

Hemocompatibility is highly affected by the flow field in Left Ventricular Assistant Devices (LVAD). An asymmetric inflow and outflow channel arrangement with a 45° intersection angle with respect to the blood chamber is proposed to approximate the vascular structure of the aorta and left atrium on the left ventricle. The structure is expected to develop uninterruptible vortex flow state which is similar to the flow state in human left ventricle. The Computational Fluid Dynamics (CFD) asymmetric model is simulated using ANSYS workbench. To validate the velocity field calculated by CFD, a Particle Image Velocimetry (PIV) experiment is conducted. The CFD results show that the proposed blood chamber could generate a shifting vortex flow that would be redirected to the aorta during ejection to form a persistent recirculating flow state, which is similar to the echocardiographic flow state in left ventricle. Both the PIV and the CFD results show the development of a persistent vortex during the pulsatile period. Comparison of the qualitative flow pattern and quantitative probed velocity histories in a pulsatile period shows a good agreement between the CFD and PIV data. The goal of developing persistent quasi intra-ventricle vortex flow state in LVAD is realized.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model

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James Vaughn Kohl

2013-06-01

Full Text Available Background: The prenatal migration of gonadotropin-releasing hormone (GnRH neurosecretory neurons allows nutrients and human pheromones to alter GnRH pulsatility, which modulates the concurrent maturation of the neuroendocrine, reproductive, and central nervous systems, thus influencing the development of ingestive behavior, reproductive sexual behavior, and other behaviors. Methods: This model details how chemical ecology drives adaptive evolution via: (1 ecological niche construction, (2 social niche construction, (3 neurogenic niche construction, and (4 socio-cognitive niche construction. This model exemplifies the epigenetic effects of olfactory/pheromonal conditioning, which alters genetically predisposed, nutrient-dependent, hormone-driven mammalian behavior and choices for pheromones that control reproduction via their effects on luteinizing hormone (LH and systems biology. Results: Nutrients are metabolized to pheromones that condition behavior in the same way that food odors condition behavior associated with food preferences. The epigenetic effects of olfactory/pheromonal input calibrate and standardize molecular mechanisms for genetically predisposed receptor-mediated changes in intracellular signaling and stochastic gene expression in GnRH neurosecretory neurons of brain tissue. For example, glucose and pheromones alter the hypothalamic secretion of GnRH and LH. A form of GnRH associated with sexual orientation in yeasts links control of the feedback loops and developmental processes required for nutrient acquisition, movement, reproduction, and the diversification of species from microbes to man. Conclusion: An environmental drive evolved from that of nutrient ingestion in unicellular organisms to that of pheromone-controlled socialization in insects. In mammals, food odors and pheromones cause changes in hormones such as LH, which has developmental affects on pheromone-controlled sexual behavior in nutrient-dependent reproductively

Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

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Vanacker, Charlotte; Moya, Manuel Ricu; DeFazio, R Anthony; Johnson, Michael L; Moenter, Suzanne M

2017-10-01

Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Copyright © 2017 Endocrine Society.

Observation of the CSF pulsatile flow in the aqueduct using cine MRI with presaturation bolus tracking, 3

International Nuclear Information System (INIS)

Nakajima, Satoshi

1992-01-01

The to-and-fro motion patterns of the CSF flow in the aqueduct in ten normal adults, ten patients with secondary normal-pressure hydrocephalus (NPH), and fourteen patients with idiopathic ventriculomegaly were analyzed using cine MRI with presaturation bolus tracking. The to-and-fro motion patterns of the CSF flow in the aqueduct were thus classified into four types according to their maximum velocity and the relative time duration of their flow in the rostral and caudal directions. The correlation between the clinical symptoms, the CT findings, the RI-cisternography findings, the results of the ICP monitorings, and the CSF pulsatile-flow patterns were then analyzed. In secondary NPH disclosing frequent B waves on ICP monitoring, the maximum velocity of the CSF flow in the aqueduct was over 15 mm/sec, and the duration of the CSF flow was longer in the caudal direction than in the rostral direction. Furthermore, the faster the maximum velocity of the CSF flow, the larger the ventricular size on CT and the more severe the CSF malabsorption on cisternography. In idiopathic ventriculomegaly, only two cases demonstrated the same CSF flow pattern as was shown in secondary NPH; the other cases demonstrated other CSF flow patterns, which were considered to indicate hydrocephalus ex vacuo or arrested hydrocephalus. The CSF pulsatile-flow pattern was assumed to change according to the degree of the CSF circulatory disorder, its compensatory process, and the plasticity of the brain. The investigation of the CSF pulsatile flow gives important information for the evaluation of various hydrocephalic conditions. (author)

Pharmacokinetic/Pharmacodynamic Modelling of GnRH Antagonist Degarelix: A Comparison of the Non-linear Mixed-Effects Programs NONMEM and NLME

DEFF Research Database (Denmark)

Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

2004-01-01

proposed by Lindstrom and Bates. The two programs were tested using clinical PK/PD data of a new gonadotropin-releasing hormone (GnRH) antagonist degarelix currently being developed for prostate cancer treatment. The pharmacokinetics of intravenous administered degarelix was analysed using a three...

Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

Energy Technology Data Exchange (ETDEWEB)

Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

1999-11-01

Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

International Nuclear Information System (INIS)

Matsuno, Y.; Yamashita, Y.; Takahashi, M.; Katabuchi, H.; Okamura, H.; Kitano, Y.; Shimamura, T.

1999-01-01

Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29±0.11). The size ratio for the hypointense tumors was 0.82±0.14, and 0.82±0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

The Role of Kiss1 Neurons As Integrators of Endocrine, Metabolic, and Environmental Factors in the Hypothalamic–Pituitary–Gonadal Axis

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Shel-Hwa Yeo

2018-04-01

Full Text Available Kisspeptin–GPR54 signaling in the hypothalamus is required for reproduction and fertility in mammals. Kiss1 neurons are key regulators of gonadotropin-releasing hormone (GnRH release and modulation of the hypothalamic–pituitary–gonadal (HPG axis. Arcuate Kiss1 neurons project to GnRH nerve terminals in the median eminence, orchestrating the pulsatile secretion of luteinizing hormone (LH through the intricate interaction between GnRH pulse frequency and the pituitary gonadotrophs. Arcuate Kiss1 neurons, also known as KNDy neurons in rodents and ruminants because of their co-expression of neurokinin B and dynorphin represent an ideal hub to receive afferent inputs from other brain regions in response to physiological and environmental changes, which can regulate the HPG axis. This review will focus on studies performed primarily in rodent and ruminant species to explore potential afferent inputs to Kiss1 neurons with emphasis on the arcuate region but also considering the rostral periventricular region of the third ventricle (RP3V. Specifically, we will discuss how these inputs can be modulated by hormonal, metabolic, and environmental factors to control gonadotropin secretion and fertility. We also summarize the methods and techniques that can be used to study functional inputs into Kiss1 neurons.

Laser Doppler anemometer measurements of pulsatile flow in a model carotid bifurcation.

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Ku, D N; Giddens, D P

1987-01-01

Hemodynamics at the human carotid bifurcation is important to the understanding of atherosclerotic plaque initiation and progression as well as to the diagnosis of clinically important disease. Laser Doppler anemometry was performed in a large scale model of an average human carotid. Pulsatile waveforms and physiologic flow divisions were incorporated. Disturbance levels and shear stresses were computed from ensemble averages of the velocity waveform measurements. Flow in the common carotid was laminar and symmetric. Flow patterns in the sinus, however, were complex and varied considerably during the cycle. Strong helical patterns and outer wall flow separation waxed and waned during each systole. The changing flow patterns resulted in an oscillatory shear stress at the outer wall ranging from -13 to 9 dyn cm-2 during systole with a time-averaged mean of only -0.5 dyn cm-2. This contrasts markedly with an inner wall shear stress range of 17-50, (mean 26) dyn cm-2. The region of transient separation was confined to the carotid sinus outer wall with no reverse velocities detected in the distal internal carotid. Notable disturbance velocities were also time-dependent, occurring only during the deceleration phase of systole and the beginning of diastole. The present pulsatile flow studies have aided in identifying hemodynamic conditions which correlate with early intimal thickening and predict the physiologic level of flow disturbances in the bulb of undiseased internal carotid arteries.

Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

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Bernd Th Krause

2009-06-01

Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

Split-time artificial insemination in beef cattle: I-Using estrous response to determine the optimal time(s) at which to administer GnRH in beef heifers and postpartum cows.

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Bishop, B E; Thomas, J M; Abel, J M; Poock, S E; Ellersieck, M R; Smith, M F; Patterson, D J

2016-09-01

Two experiments evaluated timing of GnRH administration in beef heifers and cows on the basis of estrous status during split-time artificial insemination (AI) after controlled internal drug release (CIDR) based protocols. In experiment 1, estrus was synchronized for 816 pubertal and prepubertal or peripubertal heifers using the 14-day CIDR-PGF2α (PG) protocol, and in experiment 2, estrus was synchronized for 622 lactating cows using the 7-day CO-Synch + CIDR protocol. For both experiments, estrus detection aids (Estrotect) were applied at PG, with estrus recorded at 66 and 90 hours after PG. Treatments were balanced across locations for heifers using reproductive tract score and weight; whereas for cows, treatments were assigned and balanced to treatment according to age, body condition score, and days postpartum. Timing of AI for heifers and cows was on the basis of estrus expression 66 hours after PG. Females in each treatment that exhibited estrus before 66 hours were inseminated at 66 hours, whereas AI was delayed 24 hours until 90 hours after PG for females failing to exhibit estrus before 66 hours. Females in treatment one received GnRH 66 hours after PG irrespective of estrus expression; however, in treatment 2, GnRH was administered coincident with delayed AI only to females not detected in estrus at 66 hours after PG. Among heifers, there was no effect of treatment on overall estrous response (P = 0.49) or AI pregnancy rate (P = 0.54). Pregnancy rate for heifers inseminated at 66 hours was not influenced by GnRH (P = 0.65), and there were no differences between treatments in estrous response during the 24 hours delay period (P = 0.22). Cows in treatment 2 had a greater (P = 0.04) estrous response during the 24-hour delay period resulting in a greater overall estrous response (P = 0.04), but this did not affect AI pregnancy rate at 90 hours (P = 0.51) or total AI pregnancy rate (P = 0.89). Pregnancy rate resulting from AI for

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

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Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations.

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Bruno Francou

Full Text Available CONTEXT: TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH (OMIM #146110. In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. OBJECTIVE: To evaluate the prevalence of TAC3/TACR3 mutations, characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH caused by deleterious TAC3/TACR3 biallelic mutations. RESULTS: From a cohort of 352 CHH, we selected 173 nCHH patients and identified nine patients carrying TAC3 or TACR3 variants (5.2%. We describe here 7 of these TACR3 variants (1 frameshift and 2 nonsense deleterious mutations and 4 missense variants found in 5 subjects. Modeling and functional studies of the latter demonstrated the deleterious consequence of one missense mutation (Tyr267Asn probably caused by the misfolding of the mutated NK3R protein. We found a statistically significant (p<0.0001 higher mean FSH/LH ratio in 11 nCHH patients with TAC3/TACR3 biallelic mutations than in 47 nCHH patients with either biallelic mutations in KISS1R, GNRHR, or with no identified mutations and than in 50 Kallmann patients with mutations in KAL1, FGFR1 or PROK2/PROKR2. Three patients with TAC3/TACR3 biallelic mutations had an apulsatile LH profile but low-frequency alpha-subunit pulses. Pulsatile GnRH administration increased alpha-subunit pulsatile frequency and reduced the FSH/LH ratio. CONCLUSION: The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. This ratio might be useful for pre-screening nCHH patients for TAC3/TACR3 mutations.

Prediction of low birth weight: the placental T2* estimated by MRI versus the uterine artery pulsatility index

DEFF Research Database (Denmark)

Sinding, Marianne Munk; Peters, David Alberg; Frøkjær, Jens Brøndum

(MRI) variable T2* reflects the placental oxygenation and thereby placental function. Therefore, we aimed to evaluate the performance of placental T2* in the prediction of low birth weight using the uterine artery (UtA) pulsatility index (PI) as gold standard. Methods: The study population......CONTROL ID: 2516296 ABSTRACT FINAL ID: P22.05 TITLE: Prediction of low birth weight: the placental T2* estimated by MRI versus the uterine artery pulsatility index AUTHORS (FIRST NAME, LAST NAME): Marianne Sinding1, David Peters2, Jens B. Frøkjær3, 4, Ole B. Christiansen1, 4, Astrid Petersen5...... had an EFW T2* was measured by MRI at 1.5T. A gradient recalled echo MRI sequence with readout at 16 echo times was used, and the placental T2* value was obtained by fitting the signal intensity as a function of the echo times...

Measuring pulsatile forces on the human cranium.

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Goldberg, Cory S; Antonyshyn, Oleh; Midha, Rajiv; Fialkov, Jeffrey A

2005-01-01

The cyclic stresses in the cranium caused by pulsation of the brain play an important role in the design of materials for cranioplasty, as well as craniofacial development. However, these stresses have never been quantified. In this study, the force in the epidural space against the cranium was measured intraoperatively in 10 patients using a miniature force probe. Heart and ventilatory rates computed from the force tracing correlated closely with the corresponding measured values in the patients, confirming that the forces measured were indeed a result of brain pulsation. The mean outward systolic normal and tangential stresses were 54.2 kilo-Pascals (kPa) and 345.4 kPa, respectively. The systolic shear stress was 199.8 kPa. Through mechanotransduction, these stresses play a role in cranial development. The calculated yield stress of a cranioplasty repair was 0.4 MPa, which is within one order of magnitude of the known strength of common calcium-phosphate cements. This indicates a possible relation of these pulsatile forces and occult failure of calcium-phosphate cement cranioplasties through material fatigue.

EFFECT OF GnRH AND PHOSPHORUS IN DELAYED PUBERTAL SURTI BUFFALO HEIFERS

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H.B. Dhamsaniya

2016-06-01

Full Text Available The study was conducted on eighteen delayed pubertal Surti buffalo heifers, divided into three equal groups (6 in each to evaluate the efficacy of GnRH alone and in combination of phosphorus. The buffalo heifers in Group-I and Group-II were treated with Buserelin acetate (5 ml, IM. Buffalo heifers in Group-II also received additional injection of Toldimphos sodium (10 ml, IM at 3 day interval for 4 times, while buffalo heifers in Group-III served as control. The percentage of induced estrus was highest (83.33% in each treated groups as compared to control group (50%. The mean estrus induction intervals were significantly (P<0.05 shorter in Group-I (20.20 ± 2.18 days and Group-II (18.80 ± 2.32 days as compared to control group (30.24 ± 0.81 days. The conception rate at induced estrus was highest in Group-II (50% followed by Group-I (33.33%. The plasma progesterone levels being significantly lowest on the day of estrus (less than 0.5 ng/ml as compared to pre-treatment days in all groups. The mean total protein and triglycerides levels were differed significantly between the groups on the day of estrus and being significantly higher in Group-II as compared to Group-I and III on that day. A significantly higher level of cholesterol in both treatment groups as compared to the control group during different intervals and also being higher on the day of estrus as compared to pre-treatment days. The mean plasma glucose levels were differed nonsignificantly between and within the treatment and control groups. It is concluded that estrus can be successfully induced in delayed pubertal heifers with the use of GnRH alone and in combination with phosphorus.

The pattern of LH secretion and the ovarian response to the 'ram effect' in the anoestrous ewe is influenced by body condition but not by short-term nutritional supplementation.

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Scaramuzzi, R J; Oujagir, L; Menassol, J-B; Freret, S; Piezel, A; Brown, H M; Cognié, J; Fabre Nys, C

2014-10-01

In sheep, the 'ram effect' induces out-of-season fertility and good nutrition increases prolificacy. This experiment determined if fatness or short-term nutritional supplementation modified the response to the 'ram effect'. A group of 48 Île-de-France ewes were fed diets that produced groups with body-condition scores (BCS) of >3.0 and <2.0. Within each BCS group animals were supplemented daily with 500g of lupins from Day -5 to Day 0 (ram introduction) resulting in four groups: low BCS, supplemented (n=7) and non-supplemented (n=8) and high BCS, supplemented (n=12) and non-supplemented (n=11). The blood concentrations of glucose and insulin and the LH response to gonadotrophin-releasing hormone (GnRH) were determined. After the 'ram effect' the pattern of LH pulsatility, the LH surge and ovarian responses were analysed. Low BCS ewes had lower glucose and insulin (P<0.001) and supplementation increased both (P≤0.001). The increase in LH induced by GnRH was reduced in low BCS ewes (P=0.015) but it was not affected by supplementation. Similarly, LH pulsatility was reduced in low BCS ewes (P<0.05). The LH surge and ovarian cyclicity were not affected but the follow-up cycle was delayed (P=0.034) and progesterone was reduced (P=0.029) in low BCS ewes. There was an effect of BCS on ovulation rate (P<0.05). These results show that the BCS can modify the response to the 'ram effect' and that supplementation has little effect on this response.

Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor: clinical evaluation and molecular characterization of a novel mutation.

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Frédéric Brioude

Full Text Available CONTEXT: KISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH (OMIM #146110. OBJECTIVE: To describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation. RESULTS: An original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg. In this man, pulsatile GnRH (Gonadotropin Releasing Hormone administration restored pulsatile LH (Luteinizing Hormone secretion and testicular hormone secretion. Later, long-term combined gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy. CONCLUSION: We show that a novel loss-of-function mutation (p.Tyr313His in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropin deficiency in this genetic form of nCHH.

On heat transfer to pulsatile flow of a two-phase fluid

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S. P. Chakraborty

2005-09-01

Full Text Available The problem of heat transfer to pulsatile flow of a two-phase fluid-particle system contained in a channel bounded by two infinitely long rigid impervious parallel walls has been studied in this paper. The solutions for the steady and the fluctuating temperature distributions are obtained. The rates of heat transfer at the walls are also calculated. The results are discussed numerically with graphical presentations. It is shown that the presence of the particles not only diminishes the steady and unsteady temperature fields but also decreases the reversal of heat flux at the hotter wall irrespective of the influences of other flow parameters.

Gonadotrophin-Releasing Hormone (GnRH Analogues in the Treatment of Mixed Mullerian Tumours of the Uterus: Two Case Reports and Review

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Michael Katesmark

1998-01-01

Full Text Available Subjects/Discussion. Two cases of clinical and radiological response of recurrent mixed Mullerian tumours following treatment with either nasal (Buserilin or intramuscular (Goserilin GnRH analogues are reported and a short review of the evidence to support this treatment option presented.

[Protective effect of GnRH analogues on the reproductive capacity of women with neoplasia or autoimmune disease who require chemotherapy. Final results of a phase ii clinical trial].

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Gris-Martínez, José M; Trillo-Urrutia, Lourdes; Gómez-Cabeza, Juan José; Encabo-Duró, Gloria

2016-02-05

In order to avoid the toxic effect of chemotherapy, it has been proposed to use GnRH agonist analogues (GnRHa) to inhibit the depletion of ovarian follicles. Nevertheless, there is controversy about its effectiveness. This clinical trial has been conducted with the aim to assess the protective effect of GnRH analogues on the reproductive capacity of women with malignancies or autoimmune diseases, which require chemotherapy. Open phase ii single-center clinical trial. During chemotherapy, a total of 5 doses of GnRH antagonist analogue at a dose interval of 3 days and/or a monthly dose of GnRHa were administered. Hormonal determinations prior to the start of the CT treatment were conducted during treatment and at the end of it. The inclusion of patients was prematurely concluded when incorporating the determination of anti-Müllerian hormone (AMH) as a parameter for assessing the ovarian reserve. Out of 38 patients, 23 (60.5%, 95%CI 43.4-76.0) had AMH values below normal following completion of treatment. An intermediate analysis was carried out observing that while most patients were recovering the menstrual cycle (86.6% 95%CI 71.9-95.6), they had reduced levels of AMH. Although most patients recovered their menstrual cycles, the ovarian reserve, assessed by the concentration of AMH, decreased in many patients. Therefore, we can conclude that the concomitant treatment of chemotherapy and GnRH analogues does not preserve the loss of follicular ovarian reserve. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa

DEFF Research Database (Denmark)

Støving, R K; Veldhuis, J D; Flyvbjerg, A

1999-01-01

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH...

Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.

Science.gov (United States)

Lewandowski, Krzysztof C; Cajdler-Luba, Agata; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, pPCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

Force Trends and Pulsatility for Catheter Contact Identification in Intracardiac Electrograms during Arrhythmia Ablation.

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Rivas-Lalaleo, David; Muñoz-Romero, Sergio; Huerta, Mónica; Erazo-Rodas, Mayra; Sánchez-Muñoz, Juan José; Rojo-Álvarez, José Luis; García-Alberola, Arcadi

2018-05-02

The intracardiac electrical activation maps are commonly used as a guide in the ablation of cardiac arrhythmias. The use of catheters with force sensors has been proposed in order to know if the electrode is in contact with the tissue during the registration of intracardiac electrograms (EGM). Although threshold criteria on force signals are often used to determine the catheter contact, this may be a limited criterion due to the complexity of the heart dynamics and cardiac vorticity. The present paper is devoted to determining the criteria and force signal profiles that guarantee the contact of the electrode with the tissue. In this study, we analyzed 1391 force signals and their associated EGM recorded during 2 and 8 s, respectively, in 17 patients (82 ± 60 points per patient). We aimed to establish a contact pattern by first visually examining and classifying the signals, according to their likely-contact joint profile and following the suggestions from experts in the doubtful cases. First, we used Principal Component Analysis to scrutinize the force signal dynamics by analyzing the main eigen-directions, first globally and then grouped according to the certainty of their tissue-catheter contact. Second, we used two different linear classifiers (Fisher discriminant and support vector machines) to identify the most relevant components of the previous signal models. We obtained three main types of eigenvectors, namely, pulsatile relevant, non-pulsatile relevant, and irrelevant components. The classifiers reached a moderate to sufficient discrimination capacity (areas under the curve between 0.84 and 0.95 depending on the contact certainty and on the classifier), which allowed us to analyze the relevant properties in the force signals. We conclude that the catheter-tissue contact profiles in force recordings are complex and do not depend only on the signal intensity being above a threshold at a single time instant, but also on time pulsatility and trends. These

A population of kisspeptin/neurokinin B neurons in the arcuate nucleus may be the central target of the male effect phenomenon in goats.

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Sakamoto, Kohei; Wakabayashi, Yoshihiro; Yamamura, Takashi; Tanaka, Tomomi; Takeuchi, Yukari; Mori, Yuji; Okamura, Hiroaki

2013-01-01

Exposure of females to a male pheromone accelerates pulsatile gonadotropin-releasing hormone (GnRH) secretion in goats. Recent evidence has suggested that neurons in the arcuate nucleus (ARC) containing kisspeptin and neurokinin B (NKB) play a pivotal role in the control of GnRH secretion. Therefore, we hypothesized that these neurons may be the central target of the male pheromone. To test this hypothesis, we examined whether NKB signaling is involved in the pheromone action, and whether ARC kisspeptin/NKB neurons receive input from the medial nucleus of the amygdala (MeA)--the nucleus suggested to relay pheromone signals. Ovariectomized goats were implanted with a recording electrode aimed at a population of ARC kisspeptin/NKB neurons, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA) volleys, was measured. Pheromone exposure induced an MUA volley and luteinizing hormone (LH) pulse in control animals, whereas the MUA and LH responses to the pheromone were completely suppressed by the treatment with an NKB receptor antagonist. These results indicate that NKB signaling is a prerequisite for pheromone action. In ovariectomized goats, an anterograde tracer was injected into the MeA, and possible connections between the MeA and ARC kisspeptin/NKB neurons were examined. Histochemical observations demonstrated that a subset of ARC kisspeptin/NKB neurons receive efferent projections from the MeA. These results suggest that the male pheromone signal is conveyed via the MeA to ARC kisspeptin neurons, wherein the signal stimulates GnRH pulse generator activity through an NKB signaling-mediated mechanism in goats.

Pulsatile drug delivery to ileo-colonic segments by structured incorporation of disintegrants in pH-responsive polymer coatings

NARCIS (Netherlands)

Schellekens, R.C.A.; Stellaard, F.; Mitrovic, D.; Stuurman, F.E.; Kosterink, J.G.W.; Frijlink, H.W.

2008-01-01

Conventional pH-responsive coatings used for oral drug delivery to the lower parts of the gastro-intestinal tract often show a poor performance. A new system for site-specific pulsatile delivery in the ileo-colonic regions is described. The system is based on the non-percolating incorporation of

GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines

International Nuclear Information System (INIS)

Morgan, Kevin; Meyer, Colette; Miller, Nicola; Sims, Andrew H; Cagnan, Ilgin; Faratian, Dana; Harrison, David J; Millar, Robert P; Langdon, Simon P

2011-01-01

Gonadotrophin releasing hormone (GnRH) analogs lower estrogen levels in pre-menopausal breast cancer patients. GnRH receptor (GnRH-R) activation also directly inhibits the growth of certain cells. The applicability of GnRH anti-proliferation to breast cancer was therefore analyzed. GnRH-R expression in 298 primary breast cancer samples was measured by quantitative immunofluorescence. Levels of functional GnRH-R in breast-derived cell lines were assessed using 125 I-ligand binding and stimulation of 3 H-inositol phosphate production. Elevated levels of GnRH-R were stably expressed in cells by transfection. Effects of receptor activation on in vitro cell growth were investigated in comparison with IGF-I and EGF receptor inhibition, and correlated with intracellular signaling using western blotting. GnRH-R immunoscoring was highest in hormone receptor (triple) negative and grade 3 breast tumors. However prior to transfection, functional endogenous GnRH-R were undetectable in four commonly studied breast cancer cell lines (MCF-7, ZR-75-1, T47D and MDA-MB-231). After transfection with GnRH-R, high levels of cell surface GnRH-R were detected in SVCT and MDA-MB-231 clones while low-moderate levels of GnRH-R occurred in MCF-7 clones and ZR-75-1 clones. MCF-7 sub-clones with high levels of GnRH-R were isolated following hygromycin phosphotransferase transfection. High level cell surface GnRH-R enabled induction of high levels of 3 H-inositol phosphate and modest growth-inhibition in SVCT cells. In contrast, growth of MCF-7, ZR-75-1 or MDA-MB-231 clones was unaffected by GnRH-R activation. Cell growth was inhibited by IGF-I or EGF receptor inhibitors. IGF-I receptor inhibitor lowered levels of p-ERK1/2 in MCF-7 clones. Washout of IGF-I receptor inhibitor resulted in transient hyper-elevation of p-ERK1/2, but co-addition of GnRH-R agonist did not alter the dynamics of ERK1/2 re-phosphorylation. Breast cancers exhibit a range of GnRH-R immunostaining, with higher levels of

Parity Differences in Heat Expression of Dairy Cows Synchronized with GnRH, CIDR and PGF2α during Dry Season in Zambia

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E. S. Mwaanga*, K. Choongo, H. Simukoko and C. Chama1

2012-01-01

Full Text Available A study was conducted to investigate parity differences in heat expression of dairy cows heat-synchronized during the dry season when feed scarcity is common. Cyclic cows (n=65 aged 2 to 10 years with parity range of 0 to 7 were selected from small-holder dairy farms around Lusaka. Cows were divided into 3 groups of nulliparous, primiparous and pluriparous. Heat-was synchronized using gonadotrophin releasing hormone (GnRH and controlled intra-vaginal drug releasing device (CIDR. Heat detection was observed after CIDR withdraw. The study showed a significantly (P<0.05 lower number of primiparous cows (68% coming into heat compared to nulliparous (81.8% and pluriparous cows (83.3%. It was concluded that parity influences estrus expression rate in dairy cows following synchronization with GnRH, CIDR and PGF2α during the dry season in the sub-tropics.

Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells.

Science.gov (United States)

Baird, Michelle A; Billington, Neil; Wang, Aibing; Adelstein, Robert S; Sellers, James R; Fischer, Robert S; Waterman, Clare M

2017-01-15

The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. © 2017 Baird et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Visualization and quantitative analysis of the CSF pulsatile flow with cine MR phase imaging

International Nuclear Information System (INIS)

Katayama, Shinji; Itoh, Takahiko; Kinugasa, Kazushi; Asari, Shoji; Nishimoto, Akira; Tsuchida, Shohei; Ono, Atsushi; Ikezaki, Yoshikazu; Yoshitome, Eiji.

1991-01-01

The visualization and the quantitative analysis of the CSF pulsatile flow were performed on ten healthy volunteers with cine MR phase imaging, a combination of the phase-contrast technique and the cardiac-gating technique. The velocities appropriate for the visualization and the quantitative analysis of the CSF pulsatile flow were from 6.0 cm/sec to 15.0 cm/sec. The applicability of this method for the quantitative analysis was proven with a steady-flow phantom. Phase images clearly demonstrated a to-and-fro motion of the CSF flow in the anterior subarachnoid space and in the posterior subarachnoid space. The flow pattern of CSF on healthy volunteers depends on the cardiac cycle. In the anterior subarachnoid space, the cephalic CSF flow continued until a 70-msec delay after the R-wave of the ECG and then reversed to caudal. At 130-190 msec, the caudal CSF flow reached its maximum velocity; thereafter it reversed again to cephalic. The same turn appeared following the phase, but then the amplitude decreased. The cephalic peaked at 370-430 msec, while the caudal peaked at 490-550 msec. The flow pattern of the CSF flow in the posterior subarachnoid space was almost identical to that in the anterior subarachnoid space. Cine MR phase imaging is thus useful for the visualization and the quantitative analysis of the CSF pulsative flow. (author)

Pulsatile luteinizing hormone secretion in patients with Addison's disease. Impact of glucocorticoid substitution

DEFF Research Database (Denmark)

Hangaard, J; Andersen, M; Grodum, E

1998-01-01

The physiological and pathophysiological role of cortisol in pulsatile LH release was investigated in 14 patients (5 men, 6 premenopausal women, and 3 postmenopausal women) with Addison's disease. The explicit effect of cortisol in relation to the effect of corticotropin-releasing factor (CRF......), ACTH, and opioids was ensured by hypo-, normo-, and hypercortisolism. Hypocortisolism was obtained by 24-h discontinuation of hydrocortisone (HC) followed by 23-h saline infusion. Eucortisolism was secured by infusion of HC (0.5 mg/kg) over 23 h. Stress-appropriate hypercortisolism was obtained...

GnRHR-II knockdown swine have constitutively lower serum testosterone concentrations, impaired senstitivity to GnRH analogues and reduced semen quality

Science.gov (United States)

The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are abundantly produced within swine testes. GnRHR-II localizes to porcine Leydig cells and exogenous GnRH-II treatment robustly stimulates testosterone production in vivo, despite minimal secretion of luteinizing hormo...

Enhancement of arterial pressure pulsatility by controlling continuous-flow left ventricular assist device flow rate in mock circulatory system

NARCIS (Netherlands)

Bozkurt, S.; van de Vosse, F.N.; Rutten, M.C.M.

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase

Socially regulated reproductive development: analysis of GnRH-1 and kisspeptin neuronal systems in cooperatively breeding naked mole-rats (Heterocephalus glaber).

Science.gov (United States)

Zhou, Shuzhi; Holmes, Melissa M; Forger, Nancy G; Goldman, Bruce D; Lovern, Matthew B; Caraty, Alain; Kalló, Imre; Faulkes, Christopher G; Coen, Clive W

2013-09-01

In naked mole-rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH-1-ir cell bodies do not differ between gonad-intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH-1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlying puberty or seasonal breeding in other species. Copyright © 2013 Wiley Periodicals, Inc.

The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

International Nuclear Information System (INIS)

Camats, N.; Garcia, F.; Parrilla, J.J.; Calaf, J.; Martin-Mateo, M.; Caldes, M. Garcia

2009-01-01

There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F 0 ) with reproductive parameters, and in the somatic cells of the resulting foetuses (F 1 ) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

Energy Technology Data Exchange (ETDEWEB)

Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

2009-10-02

There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

A comparative therapeutic management of anoestrus in buffaloes using insulin and GnRH

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R. D. Purkayastha

2015-06-01

Full Text Available Aim: Anoestrus is one of the most common functional disorders of the reproductive cycle in buffaloes. In spite of technical advancement, there is no single cure for the management of anoestrus. Therefore, the aim of this study was to find out the efficacy of gonadotropic releasing hormone (GnRH and metabolic hormone for the management of true anoestrus in buffaloes. Materials and Methods: The experimental animals were selected on the basis of history, gyneco-clinical examinations and progesterone estimation. Deworming was done with Fenbendazole and thereafter mineral mixture was given @ 50 g per animal per day for 10 days in all the selected buffaloes before the start of treatment. The selected buffaloes were randomly divided into four groups (n=25. In Group I, buffaloes were administered 20 μg of buserelin intramuscularly. Buffaloes of Group II were administered long-acting insulin @ 0.25 IU/Kg body weight subcutaneously for 5 consecutive days. In Group III, buffaloes were treated with a combination of insulin and buserelin in the above-mentioned doses whereas buffaloes of Group IV were kept as untreated control. Results: The higher oestrus induction (64% vs. 28% was found in Group III and differed significantly (p<0.05 as compared to control group. The conception rate (69.23% vs. 66.66% was also found higher in Group III but did not differ significantly among the treated groups. The mean time taken for the onset of oestrus was recorded significantly shorter in insulin (8.80±0.69 and GnRH (7.60±0.92 days alone and as compared to other (Group III, 14.43±0.83 and Group IV, 20.57±1.69 days groups. Conclusion: The results of this study indicated better fertility response using Insulin plus Buserelin in true anoestrus buffaloes under field conditions.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

Science.gov (United States)

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P women undergoing pituitary suppression with GnRH antagonists.

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

Science.gov (United States)

Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

A pulsatile flow model for in vitro quantitative evaluation of prosthetic valve regurgitation

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S. Giuliatti

2000-03-01

Full Text Available A pulsatile pressure-flow model was developed for in vitro quantitative color Doppler flow mapping studies of valvular regurgitation. The flow through the system was generated by a piston which was driven by stepper motors controlled by a computer. The piston was connected to acrylic chambers designed to simulate "ventricular" and "atrial" heart chambers. Inside the "ventricular" chamber, a prosthetic heart valve was placed at the inflow connection with the "atrial" chamber while another prosthetic valve was positioned at the outflow connection with flexible tubes, elastic balloons and a reservoir arranged to mimic the peripheral circulation. The flow model was filled with a 0.25% corn starch/water suspension to improve Doppler imaging. A continuous flow pump transferred the liquid from the peripheral reservoir to another one connected to the "atrial" chamber. The dimensions of the flow model were designed to permit adequate imaging by Doppler echocardiography. Acoustic windows allowed placement of transducers distal and perpendicular to the valves, so that the ultrasound beam could be positioned parallel to the valvular flow. Strain-gauge and electromagnetic transducers were used for measurements of pressure and flow in different segments of the system. The flow model was also designed to fit different sizes and types of prosthetic valves. This pulsatile flow model was able to generate pressure and flow in the physiological human range, with independent adjustment of pulse duration and rate as well as of stroke volume. This model mimics flow profiles observed in patients with regurgitant prosthetic valves.

Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana treated with a gonadotropin-releasing hormone (GnRH vaccine for inducing anoestrus

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Benavides Valades Gabriela

2012-08-01

Full Text Available Abstract Background In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Methods Between May 2009 - June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP vaccine for four years (2004-2007. Results All 12 monitored females (8 treated and 4 controls showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces were significantly higher (P Conclusions The GnRH vaccination protocol failed

Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

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Lyes eDerouiche

2015-12-01

Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals-an In Vitro and In Vivo Evaluation.

Science.gov (United States)

Biswas, Nikhil; Kuotsu, Ketousetuo

2017-02-01

The objective was to improve the dissolution of valsartan by developing valsartan nanocrystals and design a pulsed release system for the chronotherapy of hypertension. Valsartan nanocrystals were prepared by sonication-anti-solvent precipitation method and lyophilized to obtain dry powder. Nanocrystals were directly compressed to minitablets and coated to achieve pulsatile valsartan release. Pharmacokinetic profiles of optimized and commercial formulations were compared in rabbit model. The mean particle size and PDI of the optimized nanocrystal batch V4 was reported as 211 nm and 0.117, respectively. DSC and PXRD analysis confirmed the crystalline nature of valsartan in nanocrystals. The dissolution extent of valsartan was markedly enhanced with both nanocrystals and minitablets as compared to pure valsartan irrespective of pH of the medium. Core minitablet V4F containing 5% w/w polyplasdone XL showed quickest release of valsartan, over 90% within 15 min. Coated formulation CV4F showed two spikes in release profile after successive lag times of 235 and 390 min. The pharmacokinetic study revealed that the bioavailability of optimized formulation (72.90%) was significantly higher than the commercial Diovan tablet (30.18%). The accelerated stability studies showed no significant changes in physicochemical properties, release behavior, and bioavialability of CV4F formulation. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.

Biological time series analysis using a context free language: applicability to pulsatile hormone data.

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Dennis A Dean

Full Text Available We present a novel approach for analyzing biological time-series data using a context-free language (CFL representation that allows the extraction and quantification of important features from the time-series. This representation results in Hierarchically AdaPtive (HAP analysis, a suite of multiple complementary techniques that enable rapid analysis of data and does not require the user to set parameters. HAP analysis generates hierarchically organized parameter distributions that allow multi-scale components of the time-series to be quantified and includes a data analysis pipeline that applies recursive analyses to generate hierarchically organized results that extend traditional outcome measures such as pharmacokinetics and inter-pulse interval. Pulsicons, a novel text-based time-series representation also derived from the CFL approach, are introduced as an objective qualitative comparison nomenclature. We apply HAP to the analysis of 24 hours of frequently sampled pulsatile cortisol hormone data, which has known analysis challenges, from 14 healthy women. HAP analysis generated results in seconds and produced dozens of figures for each participant. The results quantify the observed qualitative features of cortisol data as a series of pulse clusters, each consisting of one or more embedded pulses, and identify two ultradian phenotypes in this dataset. HAP analysis is designed to be robust to individual differences and to missing data and may be applied to other pulsatile hormones. Future work can extend HAP analysis to other time-series data types, including oscillatory and other periodic physiological signals.

Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

DEFF Research Database (Denmark)

Juul, A; Müller, J; Skakkebaek, N E

1997-01-01

antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with Gn......RH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys....

Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect.

Science.gov (United States)

Schnerr, Roald S; Jansen, Jacobus F A; Uludag, Kamil; Hofman, Paul A M; Wildberger, Joachim E; van Oostenbrugge, Robert J; Backes, Walter H

2017-01-01

Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.

Measurement of pulsatile motion with millisecond resolution by MRI.

Science.gov (United States)

Souchon, Rémi; Gennisson, Jean-Luc; Tanter, Mickael; Salomir, Rares; Chapelon, Jean-Yves; Rouvière, Olivier

2012-06-01

We investigated a technique based on phase-contrast cine MRI combined with deconvolution of the phase shift waveforms to measure rapidly varying pulsatile motion waveforms. The technique does not require steady-state displacement during motion encoding. Simulations and experiments were performed in porcine liver samples in view of a specific application, namely the observation of transient displacements induced by acoustic radiation force. Simulations illustrate the advantages and shortcomings of the methods. For experimental validation, the waveforms were acquired with an ultrafast ultrasound scanner (Supersonic Imagine Aixplorer), and the rates of decay of the waveforms (relaxation time) were compared. With bipolar motion-encoding gradient of 8.4 ms, the method was able to measure displacement waveforms with a temporal resolution of 1 ms over a time course of 40 ms. Reasonable agreement was found between the rate of decay of the waveforms measured in ultrasound (2.8 ms) and in MRI (2.7-3.3 ms). Copyright © 2011 Wiley-Liss, Inc.

Pulsatile flow of blood and heat transfer with variable viscosity under magnetic and vibration environment

International Nuclear Information System (INIS)

Shit, G.C.; Majee, Sreeparna

2015-01-01

Unsteady flow of blood and heat transfer characteristics in the neighborhood of an overlapping constricted artery have been investigated in the presence of magnetic field and whole body vibration. The laminar flow of blood is taken to be incompressible and Newtonian fluid with variable viscosity depending upon temperature with an aim to provide resemblance to the real situation in the physiological system. The unsteady flow mechanism in the constricted artery is subjected to a pulsatile pressure gradient arising from systematic functioning of the heart and from the periodic body acceleration. The numerical computation has been performed using finite difference method by developing Crank–Nicolson scheme. The results show that the volumetric flow rate, skin-friction and the rate of heat transfer at the wall are significantly altered in the downstream of the constricted region. The axial velocity profile, temperature and flow rate increases with increase in temperature dependent viscosity, while the opposite trend is observed in the case of skin-friction and flow impedance. - Highlights: • We have investigated the pulsatile MHD flow of blood and heat transfer in arteries. • The influence of periodic body acceleration has been taken into account. • The temperature dependent viscosity of blood is considered. • The variable viscosity has an increasing effect on blood flow and heat transfer. • The overall temperature distribution enhances in the presence of magnetic field

Pulsatile flow of blood and heat transfer with variable viscosity under magnetic and vibration environment

Energy Technology Data Exchange (ETDEWEB)

Shit, G.C., E-mail: gopal_iitkgp@yahoo.co.in; Majee, Sreeparna

2015-08-15

Unsteady flow of blood and heat transfer characteristics in the neighborhood of an overlapping constricted artery have been investigated in the presence of magnetic field and whole body vibration. The laminar flow of blood is taken to be incompressible and Newtonian fluid with variable viscosity depending upon temperature with an aim to provide resemblance to the real situation in the physiological system. The unsteady flow mechanism in the constricted artery is subjected to a pulsatile pressure gradient arising from systematic functioning of the heart and from the periodic body acceleration. The numerical computation has been performed using finite difference method by developing Crank–Nicolson scheme. The results show that the volumetric flow rate, skin-friction and the rate of heat transfer at the wall are significantly altered in the downstream of the constricted region. The axial velocity profile, temperature and flow rate increases with increase in temperature dependent viscosity, while the opposite trend is observed in the case of skin-friction and flow impedance. - Highlights: • We have investigated the pulsatile MHD flow of blood and heat transfer in arteries. • The influence of periodic body acceleration has been taken into account. • The temperature dependent viscosity of blood is considered. • The variable viscosity has an increasing effect on blood flow and heat transfer. • The overall temperature distribution enhances in the presence of magnetic field.

Single and repeated GnRH agonist stimulation tests compared with basal markers of ovarian reserve in the prediction of outcome in IVF

NARCIS (Netherlands)

Hendriks, D.J.; Broekmans, F.J.M.; Bancsi, L.F.J.M.M.; Looman, C.W.N.; Jong, F.H. de; Velde, E.R. te

Purpose: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests. Methods: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed

Haploinsufficiency of Dmxl2, encoding a synaptic protein, causes infertility associated with a loss of GnRH neurons in mouse.

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Brooke Tata

2014-09-01

Full Text Available Characterization of the genetic defects causing gonadotropic deficiency has made a major contribution to elucidation of the fundamental role of Kisspeptins and Neurokinin B in puberty onset and reproduction. The absence of puberty may also reveal neurodevelopmental disorders caused by molecular defects in various cellular pathways. Investigations of these neurodevelopmental disorders may provide information about the neuronal processes controlling puberty onset and reproductive capacity. We describe here a new syndrome observed in three brothers, which involves gonadotropic axis deficiency, central hypothyroidism, peripheral demyelinating sensorimotor polyneuropathy, mental retardation, and profound hypoglycemia, progressing to nonautoimmune insulin-dependent diabetes mellitus. High-throughput sequencing revealed a homozygous in-frame deletion of 15 nucleotides in DMXL2 in all three affected patients. This homozygous deletion was associated with lower DMXL2 mRNA levels in the blood lymphocytes of the patients. DMXL2 encodes the synaptic protein rabconnectin-3α, which has been identified as a putative scaffold protein for Rab3-GAP and Rab3-GEP, two regulators of the GTPase Rab3a. We found that rabconnectin-3α was expressed in exocytosis vesicles in gonadotropin-releasing hormone (GnRH axonal extremities in the median eminence of the hypothalamus. It was also specifically expressed in cells expressing luteinizing hormone (LH and follicle-stimulating hormone (FSH within the pituitary. The conditional heterozygous deletion of Dmxl2 from mouse neurons delayed puberty and resulted in very low fertility. This reproductive phenotype was associated with a lower number of GnRH neurons in the hypothalamus of adult mice. Finally, Dmxl2 knockdown in an insulin-secreting cell line showed that rabconnectin-3α controlled the constitutive and glucose-induced secretion of insulin. In conclusion, this study shows that low levels of DMXL2 expression cause a

Implantable batteryless device for on-demand and pulsatile insulin administration

Science.gov (United States)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Flow Visualization of Three-Dimensionality Inside the 12 cc Penn State Pulsatile Pediatric Ventricular Assist Device

OpenAIRE

Roszelle, Breigh N.; Deutsch, Steven; Manning, Keefe B.

2010-01-01

In order to aid the ongoing concern of limited organ availability for pediatric heart transplants, Penn State has continued development of a pulsatile Pediatric Ventricular Assist Device (PVAD). Initial studies of the PVAD observed an increase in thrombus formation due to differences in flow field physics when compared to adult sized devices, which included a higher degree of three-dimensionality. This unique flow field brings into question the use of 2D planar particle image velocimetry (PIV...

Gonadotropin Releasing Hormone (GnRH) Neuron Migration: Initiation, Maintenance and Cessation as Critical Steps to Ensure Normal Reproductive Function

OpenAIRE

Wierman, Margaret E.; Kiseljak-Vassiliades, Katja; Tobet, Stuart

2010-01-01

GnRH neurons follow a carefully orchestrated journey from their birth in the olfactory placode area. Initially, they migrate along with the vomeronasal nerve into the brain at the cribriform plate, then progress caudally to sites within the hypothalamus where they halt and send projections to the median eminence to activate pituitary gonadotropes. Many factors controlling this precise journey have been elucidated by the silencing or over expression of candidate genes in mouse models. Importan...

Control of the onset of puberty.

Science.gov (United States)

Livadas, Sarantis; Chrousos, George P

2016-08-01

The mechanism of puberty initiation remains an enigma, despite extensive research in the field. Pulsatile pituitary gonadotropin secretion under the guidance of hypothalamic gonadotropin-releasing hormone (GnRH) constitutes a sine qua non for pubertal onset. In turn, the secretion of GnRH in the human hypothalamus is regulated by kisspeptin and its receptor as well as by permissive or opposing signals mediated by neurokinin B and dynorphin acting on their respective receptors. These three supra-GnRH regulators compose the Kisspeptin, Neurokinin B and Dynorhin neurons (KNDy) system, a key player in pubertal onset and progression. The recent discovery that makorin ring finger protein 3 is also involved in puberty initiation provided further insights into the regulation of the KNDy pathway. In fact, the inhibitory (γ-amino butyric acid, neuropeptide Y, and RFamide-related peptide-3) and stimulatory signals (glutamate) acting upstream of KNDy called into question the role of makorin ring finger protein 3 as the gatekeeper of puberty. Meanwhile, the findings that 'neuroestradiol' produced locally and endocrine disruptors from the environment may influence GnRH secretion is intriguing. Finally, epigenetic mechanisms have been implicated in pubertal onset through recently discovered mechanisms. The exact molecular machinery underlying puberty initiation in humans is under intensive investigation. In this review, we summarize research evidence in the field, while emphasizing the areas of uncertainty and underlining the impact of current information on the evolving theory regarding this fascinating phenomenon.

Pulsatile flow of viscous and viscoelastic fluids in constricted tubes

Energy Technology Data Exchange (ETDEWEB)

Javadzadegan, A.; Esmaeili, M.; Majidi, S. [University of Tehran, Tehran (Iran, Islamic Republic of); Fakhimghanbarzadeh, B. [Sharif University of Technology, Tehran (Iran, Islamic Republic of)

2009-09-15

The unsteady flow of blood through stenosed artery, driven by an oscillatory pressure gradient, is studied. An appropriate shape of the time-dependent stenoses which are overlapped in the realm of the formation of arterial narrowing is constructed mathematically. A mathematical model is developed by treating blood as a non-Newtonian fluid characterized by the Oldroyd-B and Cross models. A numerical scheme has been used to solve the unsteady nonlinear Navier- stokes equations in cylindrical coordinate system governing flow, assuming axial symmetry under laminar flow condition so that the problem effectively becomes two-dimensional. Finite difference technique was used to investigate the effects of parameters such as pulsatility, non-Newtonian properties and the flow time on the velocity components, the rate of flow, and the wall shear stress through their graphical representations quantitatively at the end of the paper in order to validate the applicability of the present improved mathematical model under consideration

Pulsatile flow of viscous and viscoelastic fluids in constricted tubes

International Nuclear Information System (INIS)

Javadzadegan, A.; Esmaeili, M.; Majidi, S.; Fakhimghanbarzadeh, B.

2009-01-01

The unsteady flow of blood through stenosed artery, driven by an oscillatory pressure gradient, is studied. An appropriate shape of the time-dependent stenoses which are overlapped in the realm of the formation of arterial narrowing is constructed mathematically. A mathematical model is developed by treating blood as a non-Newtonian fluid characterized by the Oldroyd-B and Cross models. A numerical scheme has been used to solve the unsteady nonlinear Navier- stokes equations in cylindrical coordinate system governing flow, assuming axial symmetry under laminar flow condition so that the problem effectively becomes two-dimensional. Finite difference technique was used to investigate the effects of parameters such as pulsatility, non-Newtonian properties and the flow time on the velocity components, the rate of flow, and the wall shear stress through their graphical representations quantitatively at the end of the paper in order to validate the applicability of the present improved mathematical model under consideration

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

Science.gov (United States)

Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

2017-06-01

This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged 0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

Estrogen modulates potassium currents and expression of the Kv4.2 subunit in GT1-7 cells.

Science.gov (United States)

Farkas, Imre; Varju, Patricia; Liposits, Zsolt

2007-03-01

The proper maintenance of reproduction requires the pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is ensured by synchronized periodic firing of multiple GnRH neurons. Both hormone secretion and electrophysiological properties of GnRH cells are influenced by estrogen. The impact of 17beta-estradiol treatment on the function of voltage gated A- and K-type potassium channels, known modulators of firing rate, was therefore examined in our experiments using immortalized GnRH-producing GT1-7 neurons. Whole cell patch clamp recordings showed the absence of the A-type current in GT1-7 cells cultured in estrogen-free medium and after 8h 17beta-estradiol treatment. Exposure of the cells to 17beta-estradiol for 24 and 48 h, respectively, resulted in the appearance of the A-type current. The induction of the A-type current by 17beta-estradiol was dose-related (50 pM to 15 nM range). In contrast, the K-type potassium current was apparent in the estrogen-free environment and 17beta-estradiol administration significantly decreased its amplitude. Co-administration of 17beta-estradiol and estrogen receptor blocker, Faslodex (ICI 182,780; 1 microM) abolished the occurrence of the A-type current. Real-time PCR data demonstrated that expression of the Kv4.2 subunit of the A-type channel was low at 0, 0.5, 2 and 8h, peaked at 24h and diminished at 48 h 17beta-estradiol treatment (15 nM). These data indicate that potassium channels of GT1-7 neurons are regulated by estrogen a mechanism that might contribute to modulation of firing rate and hormone secretion in GnRH neurons.

Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy

NARCIS (Netherlands)

I.M. van der Sluis (Inge); A.M. Boot (Annemieke); E.P. Krenning (Eric); S.L.S. Drop (Stenvert); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

2002-01-01

textabstractWe studied bone mineral density (BMD), bone metabolism, and body composition in 47 children with central precocious puberty (n = 36) or early puberty (n = 11) before, during, and after cessation of GnRH agonist. Bone density and body composition were measured with dual

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

Directory of Open Access Journals (Sweden)

Georg Griesinger

Full Text Available What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS based on the number of growing follicles ≥ 11 mm and/or estradiol (E2 levels?The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2 levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.In comparison to long gonadotropin-releasing hormone (GnRH agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF, while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years IVF population treated in a GnRH-antagonist protocol.From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH in a gonadotropin-releasing hormone (GnRH-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG, and a combination of both, were determined.The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at

Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy

International Nuclear Information System (INIS)

Farzam, Parisa; Zirak, Peyman; Durduran, Turgut; Binzoni, Tiziano

2013-01-01

The cardiac cycle related pulsatile behavior of the absorption and scattering coefficients of diffuse light and the corresponding alterations in hemoglobin concentrations in the human patella was studied. The pulsations in scattering is considerably smaller than absorption. The difference in amplitude of absorption coefficient pulsations for different wavelengths was translated to pulsations in oxygenated and deoxygenated hemoglobin, which leads to strong pulsations in the total hemoglobin concentration and oxygen saturation. The physiological origin of the observed signals was confirmed by applying a thigh-cuff. Moreover, we have investigated the optical and physiological properties of the patella bone and their changes in response to arterial cuff occlusion. (paper)

Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy.

Science.gov (United States)

Farzam, Parisa; Zirak, Peyman; Binzoni, Tiziano; Durduran, Turgut

2013-08-01

The cardiac cycle related pulsatile behavior of the absorption and scattering coefficients of diffuse light and the corresponding alterations in hemoglobin concentrations in the human patella was studied. The pulsations in scattering is considerably smaller than absorption. The difference in amplitude of absorption coefficient pulsations for different wavelengths was translated to pulsations in oxygenated and deoxygenated hemoglobin, which leads to strong pulsations in the total hemoglobin concentration and oxygen saturation. The physiological origin of the observed signals was confirmed by applying a thigh-cuff. Moreover, we have investigated the optical and physiological properties of the patella bone and their changes in response to arterial cuff occlusion.

Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism

Directory of Open Access Journals (Sweden)

Chen-Xi Li

2015-01-01

Full Text Available To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45% than the control subjects (10.00% (P<0.001. The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (P<0.001, for all and higher fasting insulin (P=0.001, HOMA-IR (P=0.002, and SHBG (P<0.001 compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI (P=0.021 and BMD in lumbar spine 2–4, femoral neck, and total hip (P=0.002, P=0.003, and P=0.003, resp. increased dramatically and total cholesterol (P=0.034, fasting insulin (P=0.025, HOMA-IR (P=0.021, and SHBG (P=0.001 decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients.

Assessment of turbulence models for pulsatile flow inside a heart pump.

Science.gov (United States)

Al-Azawy, Mohammed G; Turan, A; Revell, A

2016-02-01

Computational fluid dynamics (CFD) is applied to study the unsteady flow inside a pulsatile pump left ventricular assist device, in order to assess the sensitivity to a range of commonly used turbulence models. Levels of strain and wall shear stress are directly relevant to the evaluation of risk from haemolysis and thrombosis, and thus understanding the sensitivity to these turbulence models is important in the assessment of uncertainty in CFD predictions. The study focuses on a positive displacement or pulsatile pump, and the CFD model includes valves and moving pusher plate. An unstructured dynamic layering method was employed to capture this cyclic motion, and valves were simulated in their fully open position to mimic the natural scenario, with in/outflow triggered at control planes away from the valves. Six turbulence models have been used, comprising three relevant to the low Reynolds number nature of this flow and three more intended to investigate different transport effects. In the first group, we consider the shear stress transport (SST) [Formula: see text] model in both its standard and transition-sensitive forms, and the 'laminar' model in which no turbulence model is used. In the second group, we compare the one equation Spalart-Almaras model, the standard two equation [Formula: see text] and the full Reynolds stress model (RSM). Following evaluation of spatial and temporal resolution requirements, results are compared with available experimental data. The model was operated at a systolic duration of 40% of the pumping cycle and a pumping rate of 86 BPM (beats per minute). Contrary to reasonable preconception, the 'transition' model, calibrated to incorporate additional physical modelling specifically for these flow conditions, was not noticeably superior to the standard form of the model. Indeed, observations of turbulent viscosity ratio reveal that the transition model initiates a premature increase of turbulence in this flow, when compared with

Incidence of premature estrus in lactating dairy cows and conception rates to standing estrus or fixed-time inseminations after synchronization using GnRH and PGF(2alpha).

Science.gov (United States)

DeJarnette, J M; Salverson, R R; Marshall, C E

2001-07-03

Fixed-time AI (TAI) after GnRH-PGF(2alpha)-GnRH treatment is a method to achieve pregnancies in dairy herds without estrous detection. However, cows that fail to respond to the initial GnRH may have compromised TAI conception rates due to asynchronous ovarian response. This study documented the percentage of GnRH-treated Holstein cows (n=345) in two herds that displayed estrus at an inopportune time for optimum TAI conception rate (conception rates of two TAI protocols in cows that did not display PE. At biweekly herd health exams, cows diagnosed as not pregnant to a previous AI and cows >80 days postpartum with no AI were treated with 100 microg GnRH (day -7) and 25mg PGF(2alpha) (day 0). Cows detected in PE by twice-daily visual observation from day -7 to day 2 were bred by AI 8-12h later. Cows not detected in PE were randomly assigned by parity, body condition score, and postpartum interval to receive either: (1) 100microg GnRH at 48h after PGF(2alpha) and TAI 16 to 18h later (Ovsynch); or (2) TAI at 72h post-PGF(2alpha) and a concurrent 100 microg GnRH injection to those cows not detected in estrus between 48 and 72h post-PGF(2alpha) (modified Ovsynch (MOV)). All hormone injections were im. Twenty percent (68/345) of the cows were detected in estrus before 48 after PGF(2alpha), of which 5% (17/345) were detected in estrus before PGF(2alpha) (Conception rates were not affected by treatment (PE versus Ovsynch versus MOV; 32% (21/65) versus 30% (37/125) versus 32% (47/145); P>0.10). However, within MOV-treated cows, conception rates were greater (Prates are to be achieved. Although additional estrous detection is required compared to Ovsynch, reduced cow handling and hormone usage, efficient use of expensive semen through greater conception rates in cows detected in estrus, and comparable TAI conception rates, suggests the MOV protocol may be a cost effective alternative to Ovsynch in many dairy herd reproductive management programs.

Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana) treated with a gonadotropin-releasing hormone (GnRH) vaccine for inducing anoestrus.

Science.gov (United States)

Benavides Valades, Gabriela; Ganswindt, Andre; Annandale, Henry; Schulman, Martin L; Bertschinger, Henk J

2012-08-25

In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH) vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Between May 2009-June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM) on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa) 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP) vaccine for four years (2004-2007). All 12 monitored females (8 treated and 4 controls) showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces) were significantly higher (Pelephants. These results indicate that irregular oestrous cycles occur amongst free

Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

Science.gov (United States)

Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

2008-07-01

States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Comparison between induction effect with pulsatile and continuous oxytocin administration on outcomes of pregnancy in the pregnant women referring to Tabriz 29 Bahman hospital in 2006

Directory of Open Access Journals (Sweden)

fahimeh Sehhati

2008-04-01

Full Text Available Abstract Background: Insufficient uterine activity or hypotonic uterine contraction is a common reason and the cause of abnormal labor progress that can be corrected with oxytocin. Realizing this fact that undue prolongation of labor may contribute to prenatal morbidity has resulted in using oxytocin infusion in different kinds of ineffective uterine contractions. Materials and methods: In this study, one hundred pregnant women in 29 Bahman hospital participated in a quasi-experimental research and were divided randomly into 2 groups of pulsatile induction as well as continuous induction and were compared in terms of pregnancy outcomes including progress of labor, hyperstimulation, mood of delivery, third stage duration, newborn’s Apgar score, and hyperbilirobinemia. Results: There were no significant differences between the two groups in progress of labor, hyperstimulation rate, newborn’s Apgar score, and hyperbilirobinemia (p>0.05 however, significant differences were observed in labor duration (p=0.022, mood of delivery (p=0.008, and dose of oxytocin (p<0.0005. Conclusion: According to the findings of this study, administration of oxytocin with the feedback pulsatile oxytocin system is easier and more physiologic to establish the effective uterine contraction and reduces duration of labor and cesarean section rate. Moreover, the average dose of oxytocin administered is significantly less in the pulsatile induction group.

A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.

Science.gov (United States)

Jacob, S L; Brewer, C; Tang, T; Picton, H M; Barth, J H; Balen, A H

2016-12-01

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle? A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or

PLATELET ADHESION TO POLYURETHANE UREA UNDER PULSATILE FLOW CONDITIONS

Science.gov (United States)

Navitsky, Michael A.; Taylor, Joshua O.; Smith, Alexander B.; Slattery, Margaret J.; Deutsch, Steven; Siedlecki, Christopher A.; Manning, Keefe B.

2014-01-01

Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s−1. The aim of the current work is to determine platelet adhesion properties to the polyurethane urea surface as a function of time varying shear exposure. A rotating disk system is used to study the influence of steady and pulsatile flow conditions (e.g. cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments retain the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk is rotated in platelet rich bovine plasma for two hours with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow is found to exponentially decay with increasing shear rate. Adhesion levels are found to depend upon peak platelet flux and shear rate regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices. PMID:24721222

Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

International Nuclear Information System (INIS)

Rettori, V.; McCann, S.M.; Gimeno, M.F.; Karara, A.; Gonzalez, M.C.

1991-01-01

Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E 2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E 2 -mediated release of LHRH

Evidence That Dopamine Acts via Kisspeptin to Hold GnRH Pulse Frequency in Check in Anestrous Ewes

Science.gov (United States)

Maltby, Matthew J.; Millar, Robert P.; Hileman, Stanley M.; Nestor, Casey C; Whited, Brant; Tseng, Ashlie S.; Coolen, Lique M.; Lehman, Michael N.

2012-01-01

Recent work has implicated stimulatory kisspeptin neurons in the arcuate nucleus (ARC) as important for seasonal changes in reproductive function in sheep, but earlier studies support a role for inhibitory A15 dopaminergic (DA) neurons in the suppression of GnRH (and LH) pulse frequency in the nonbreeding (anestrous) season. Because A15 neurons project to the ARC, we performed three experiments to test the hypothesis that A15 neurons act via ARC kisspeptin neurons to inhibit LH in anestrus: 1) we used dual immunocytochemistry to determine whether these ARC neurons contain D2 dopamine receptor (D2-R), the receptor responsible for inhibition of LH in anestrus; 2) we tested the ability of local administration of sulpiride, a D2-R antagonist, into the ARC to increase LH secretion in anestrus; and 3) we determined whether an antagonist to the kisspeptin receptor could block the increase in LH secretion induced by sulpiride in anestrus. In experiment 1, 40% of this ARC neuronal subpopulation contained D2-R in breeding season ewes, but this increased to approximately 80% in anestrus. In experiment 2, local microinjection of the two highest doses (10 and 50 nmol) of sulpiride into the ARC significantly increased LH pulse frequency to levels 3 times that seen with vehicle injections. Finally, intracerebroventricular infusion of a kisspeptin receptor antagonist completely blocked the increase in LH pulse frequency induced by systemic administration of sulpiride to anestrous ewes. These results support the hypothesis that DA acts to inhibit GnRH (and LH) secretion in anestrus by suppressing the activity of ARC kisspeptin neurons. PMID:23038740

Degarelix: A Novel Gonadotropin-Releasing Hormone (GnRH) Receptor Blocker-Results from a 1-yr, Multicentre, Randomised, Phase 2 Dosage-Finding Study in the Treatment of Prostate Cancer

NARCIS (Netherlands)

van Poppel, Hendrik; Tombal, Bertrand; de la Rosette, Jean J.; Persson, Bo-Eric; Jensen, Jens-Kristian; Kold Olesen, Tine

2008-01-01

Background: Degarelix is a gonadotropin-releasing hormone antagonist (GnRH receptor blocker) with immediate onset of action, suppressing gonadotropins, testosterone, and prostate-specific antigen (PSA) in prostate cancer. Objective: To determine the efficacy and safety of initial doses of 200 mg or

Comparison of GnRh Agonist Microdose Flare Up and GnRh Antagonist/Letrozole in Treatment of Poor Responder Patients in Intra Cytoplaspic Sperm Injection: Randomized Clinical Trial.

Science.gov (United States)

Nabati, Azar; Peivandi, Sepideh; Khalilian, Alireza; Mirzaeirad, Sina; Hashemi, Seyyed Abbas

2015-08-06

the prevalence of infertility is up to 10 to 15 % which 9 to 24 % of them are Poor Ovarian Responders (POR). This study was designed to compare two methods of GnRH Agonist Microdose Flareup (MF) and GnRH Antagonist/Letrozole (AL) in treatment of these patients. this randomized clinical trial study consisted of 123 patients. In the first step of treatment in both methods FSH, LH, estradiol, anderostandion, testestron in third day of menstruation period and the thickness of endometrium by Transvaginal sonography were evaluated. At the time of HCG injection the thickness of endometrium and follicles which were more than 14mm ware established and hormones were evaluated. Two weeks later serum βhCG and after 6 to 8 weeks Transvaginal sonography were applied to prove the pregnancy. there were 61 patients with mean age of 38.7±4.58 in MF group and 62 patients with mean age of 38.5±4.6 in AL group (P=0.80). At the time of hCG injection there were significant increase in the level of LH,estradiol, thickness of endometrium and follicles more than 14mm in MF patients (P<0.0001). The mean time of ovary stimulation in MF group was 10.72±1.5 and in AL was 8.45±1.2 (P<0.0001). The mean level of gonadotropin which were used was 80.6±20.1 in MF patients and 64.7±16.4 in AL group (P<0.0001). 18 % of MF group and 38.7% in AL group had no normal cycle of ovulation (OR: 2.87, 95% CI: 1.25-6.57, P=0.011). The mean numbers of oocyte and normal fetus in MF was 5.83±3.5 and 3.7±2.5 and in AL was 3±1.69 and 1.4±1.33 (P<0.0001). The number of chemical pregnancy in MF group was 10 (16.4%) and in AL was 3 (4.8%) (OR:3.85, 95%CI:1.06-14.77, P=0.037). Clinical pregnancy in 10 patients (16.4%) of MF group and 3 (4.8%)in AL was reported. OR: 3.85, 95%CI: 1.06-14.77, P=0.037). this study showed that MF method of pregnancy leads to more positive results in pregnancy based on chemical and clinical evaluation in comparison with AL and is advised for poor responder patients.

Non-invasive estimation of pulsatile flow and differential pressure in an implantable rotary blood pump for heart failure patients

International Nuclear Information System (INIS)

AlOmari, A H; Savkin, A V; Karantonis, D M; Lim, E; Lovell, N H

2009-01-01

We propose dynamical models for pulsatile flow and head estimation in an implantable rotary blood pump. Pulsatile flow and head data were obtained using a circulatory mock loop where fluid solutions with different values of viscosities were used as a blood analogue with varying haematocrit (HCT). Noninvasive measurements of power and pump speed were used with HCT values as inputs to the flow model while the estimated flow was used with the speed as inputs to a head estimation model. Linear regression analysis between estimated and measured flows obtained from a mock loop resulted in a highly significant correlation (R 2 = 0.982) and a mean absolute error (e) of 0.323 L min −1 , while for head, R 2 = 0.933 and e = 7.682 mmHg were obtained. R 2 = 0.849 and e = 0.584 L min −1 were obtained when the same model derived in the mock loop was used for flow estimation in ex vivo porcine data (N = 6). Furthermore, in the steady state, the solution of the presented flow model can be described by a previously designed and verified static model. The models developed herein will play a vital role in developing a robust control system of the pump flow coping with changing physiological demands

Experimental and theoretical investigations of Lantana camara oil diffusion from polyacrylonitrile membrane for pulsatile drug delivery system

Energy Technology Data Exchange (ETDEWEB)

Verma, Vivek [Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune 411008 (India); Balasubramanian, K., E-mail: meetkbs@gmail.com [Department of Materials Engineering, Defence Institute of Advance Technology (DIAT), Ministry of Defence, Girinagar, Pune 411025 (India)

2014-08-01

Porous composite membrane of polyacrylonitrile (PAN) and Lantana camara essential oil was synthesized by solvent casting method. Stability of oil in PAN solution was measured by XiGo nano tool indicating constant relaxation time of 1487 time/s. Pore size of few microns confirmed by electron microscopy was supported by atomic force microscopy indicating roughness factor of 0.9 nm. Contact angle of 2° inveterates superhydrophilicity of the composite membrane. Membrane showed excellent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli with a 7–10 mm zone of inhibition. In vitro release of Lantana oil from the composite membrane was carried out in isotonic phosphate buffer solution (pH = 7.4). Lantana oil was released for 9 h, lag time of 3 h with constant 33% release confirmed PAN membranes as potential system for pulsatile drug delivery applications. Diffusion of E-caryophyllene (antibacterial component of oil) which was studied through molecular simulation using Material Studio software ensued diffusion coefficient value of 1.11 ∗ 10{sup −9} m{sup 2}/s. Biocompatibility of the composite membrane was assessed by mouse embryonic fibroblast cell line (NIH 3T3) through MTT assay indicating more than 91% viable cell even at 200 μg/mL concentration. Such membranes can be efficiently used in biomedical applications as antibacterial and antifungal agent. - Highlights: • Pulsatile release • Lantana oil–PAN composite membrane as antibacterial material • Enhanced bactericidal activity of the membrane.

Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells

DEFF Research Database (Denmark)

Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex

2012-01-01

in comparison with endothelial cells grown under static conditions. There was a significant association between the expression of TRPC6 and tumor necrosis factor-α mRNA in human vascular tissue. No-flow and atheroprone flow conditions are equally characterized by an increase in the expression of tumor necrosis......The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined...

The IVF Outcome Counseling Based on the Model Combining DHEAS and Age in Patients with Low AMH Prior to the First Cycle of GnRH Antagonist Protocol of Ovarian Stimulation

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Miro Šimun Alebić

2013-01-01

Full Text Available Objective. To investigate the endocrine and/or clinical characteristics of women with low anti-Müllerian hormone (AMH that could improve the accuracy of IVF outcome prediction based on the female age alone prior to the first GnRH antagonist IVF cycle. Methods. Medical records of 129 patients with low AMH level (<6.5 pmol/L who underwent their first GnRH antagonist ovarian stimulation protocol for IVF/ICSI were retrospectively analyzed. The main outcome measure was the area under the ROC curve (AUC-ROC for the models combining age and other potential predictive factors for the clinical pregnancy. Results. Clinical pregnancy rate (CPR per initiated cycles was 11.6%. For the prediction of clinical pregnancy, DHEAS and age showed AUC-ROC of 0.726 (95%CI 0.641–0.801 and 0.662 (95%CI 0.573–0.743, respectively (. The predictive accuracy of the model combining age and DHEAS (AUC-ROC 0.796; 95%CI 0.716–0.862 was significantly higher compared to that of age alone (. In patients <37.5 years with DHEAS  pmol/L, 60% (9/15 of all pregnancies were achieved with CPR of 37.5%. Conclusions. DHEAS appears to be predictive for clinical pregnancy in younger women (<37.5 years with low AMH after the first GnRH antagonist IVF cycle. Therefore, DHEAS-age model could refine the pretreatment counseling on pregnancy prospects following IVF.

Reference Curve for the Mean Uterine Artery Pulsatility Index in Singleton Pregnancies.

Science.gov (United States)

Weichert, Alexander; Hagen, Andreas; Tchirikov, Michael; Fuchs, Ilka B; Henrich, Wolfgang; Entezami, Michael

2017-05-01

Doppler sonography of the uterine artery (UA) is done to monitor pregnancies, because the detected flow patterns are useful to draw inferences about possible disorders of trophoblast invasion. Increased resistance in the UA is associated with an increased risk of preeclampsia and/or intrauterine growth restriction (IUGR) and perinatal mortality. In the absence of standardized figures, the normal ranges of the various available reference curves sometimes differ quite substantially from one another. The causes for this are differences in the flow patterns of the UA depending on the position of the pulsed Doppler gates as well as branching of the UA. Because of the discrepancies between the different reference curves and the practical problems this poses for guideline recommendations, we thought it would be useful to create our own reference curves for Doppler measurements of the UA obtained from a singleton cohort under standardized conditions. This retrospective cohort study was carried out in the Department of Obstetrics of the Charité - Universitätsmedizin Berlin, the Department for Obstetrics and Prenatal Medicine of the University Hospital Halle (Saale) and the Center for Prenatal Diagnostics and Human Genetics Kurfürstendamm 199. Available datasets from the three study locations were identified and reference curves were generated using the LMS method. Measured values were correlated with age of gestation, and a cubic model and Box-Cox power transformation (L), the median (M) and the coefficient of variation (S) were used to smooth the curves. 103 720 Doppler examinations of the UA carried out in singleton pregnancies from the 11th week of gestation (10 + 1 GW) were analyzed. The mean pulsatility index (Mean PI) showed a continuous decline over the course of pregnancy, dropping to a plateau of around 0.84 between the 23rd and 27th GW, after which it decreased again. Age of gestation, placental position, position of pulsed Doppler gates and branching of

EIT based pulsatile impedance monitoring during spontaneous breathing in cystic fibrosis.

Science.gov (United States)

Krueger-Ziolek, Sabine; Schullcke, Benjamin; Gong, Bo; Müller-Lisse, Ullrich; Moeller, Knut

2017-06-01

Evaluating the lung function in patients with obstructive lung disease by electrical impedance tomography (EIT) usually requires breathing maneuvers containing deep inspirations and forced expirations. Since these maneuvers strongly depend on the patient's co-operation and health status, normal tidal breathing was investigated in an attempt to develop continuous maneuver-free measurements. Ventilation related and pulsatile impedance changes were systematically analyzed during normal tidal breathing in 12 cystic fibrosis (CF) patients and 12 lung-healthy controls (HL). Tidal breaths were subdivided into three inspiratory (In1, In2, In3) and three expiratory (Ex1, Ex2, Ex3) sections of the same amplitude of global impedance change. Maximal changes of the ventilation and the pulsatile impedance signal occurring during these sections were determined (▵I V and ▵I P ). Differences in ▵I V and ▵I P among sections were ascertained in relation to the first inspiratory section. In addition, ▵I V /▵I P was calculated for each section. Medians of changes in ▵I V were  <0.05% in all sections for both subject groups. Both groups showed a similar pattern of ▵I P changes during tidal breathing. Changes in ▵I P first decreased during inspiration (In2), then increased towards the end of inspiration (In3) and reached a maximum at the beginning of expiration (Ex1). During the last two sections of expiration (Ex2, Ex3) ▵I P changes decreased. The CF patients showed higher variations in ▵I P changes compared to the controls (CF:  -426.5%, HL:  -158.1%, coefficient of variation). Furthermore, ▵I V /▵I P significantly differed between expiratory sections for the CF patients (Ex1-Ex2, p  <  0.01; Ex1-Ex3, p  <  0.001; Ex2-Ex3, p  <  0.05), but not for the controls. No significant differences in ▵I V /▵I P between inspiratory sections were determined for both groups. Differences in ▵I P changes and in ▵I V /▵I P between

Outpatient management of severe early OHSS by administration of GnRH antagonist in the luteal phase: an observational cohort study

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Lainas George T

2012-08-01

Full Text Available Abstract Background Management of established severe OHSS requires prolonged hospitalization, occasionally in intensive care units, accompanied by multiple ascites punctures, correction of intravascular fluid volume and electrolyte imbalance. The aim of the present study was to evaluate whether it is feasible to manage women with severe OHSS as outpatients by treating them with GnRH antagonists in the luteal phase. Methods This is a single-centre, prospective, observational, cohort study. Forty patients diagnosed with severe OHSS, five days post oocyte retrieval, were managed as outpatients after administration of GnRH antagonist (0.25 mg daily from days 5 to 8 post oocyte retrieval, combined with cryopreservation of all embryos. The primary outcome measure was the proportion of patients with severe OHSS, in whom outpatient management was not feasible. Results 11.3% (95% CI 8.3%-15.0% of patients (40/353 developed severe early OHSS. None of the 40 patients required hospitalization following luteal antagonist administration and embryo cryopreservation. Ovarian volume, ascites, hematocrit, WBC, serum oestradiol and progesterone decreased significantly (P  Conclusions The current study suggests, for the first time, that successful outpatient management of severe OHSS with antagonist treatment in the luteal phase is feasible and is associated with rapid regression of the syndrome, challenging the dogma of inpatient management. The proposed management is a flexible approach that minimizes unnecessary embryo transfer cancellations in the majority (88.7% of high risk for OHSS patients.

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

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Mahbod Ebrahimi

2017-08-01

Full Text Available Background: Gonadotropin-releasing hormone (GnRH antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. Objective: The object of this study was to evaluate the efficacy of letrozole cotreatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection. Materials and Methods: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA group and placebo+GnRH-antagonist (PA group (n=35/each. The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate. Results: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81, number of embryos transferred (p=0.82, fertilization rate (p=0.225, implantation rate (p=0.72, total cycle cancelation rate (p=0.08, and clinical pregnancy rate (p=0.12. Conclusion: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.

Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized Based on a Correlation Mapping Technique.

Science.gov (United States)

Yatsushiro, Satoshi; Sunohara, Saeko; Hayashi, Naokazu; Hirayama, Akihiro; Matsumae, Mitsunori; Atsumi, Hideki; Kuroda, Kagayaki

2018-04-10

A correlation mapping technique delineating delay time and maximum correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation was proposed. After proofing its technical concept, this technique was applied to healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients. A time-resolved three dimensional-phase contrast (3D-PC) sampled the cardiac-driven CSF velocity at 32 temporal points per cardiac period at each spatial location using retrospective cardiac gating. The proposed technique visualized distributions of propagation delay and correlation coefficient of the PC-based CSF velocity waveform with reference to a waveform at a particular point in the CSF space. The delay time was obtained as the amount of time-shift, giving the maximum correlation for the velocity waveform at an arbitrary location with that at the reference location. The validity and accuracy of the technique were confirmed in a flow phantom equipped with a cardiovascular pump. The technique was then applied to evaluate the intracranial CSF motions in young, healthy (N = 13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13). The phantom study demonstrated that root mean square error of the delay time was 2.27%, which was less than the temporal resolution of PC measurement used in this study (3.13% of a cardiac cycle). The human studies showed a significant difference (P correlation coefficient between the young, healthy group and the other two groups. A significant difference (P correlation coefficients in intracranial CSF space among all groups. The result suggests that the CSF space compliance of iNPH patients was lower than that of healthy volunteers. The correlation mapping technique allowed us to visualize pulsatile CSF velocity wave propagations as still images. The technique may help to classify diseases related to CSF dynamics, such as iNPH.

Experience With a Long-term Pulsatile Ventricular Assist Device as a Bridge to Heart Transplant in Adults.

Science.gov (United States)

Gómez Bueno, Manuel; Segovia Cubero, Javier; Serrano Fiz, Santiago; Ugarte Basterrechea, Juan; Hernández Pérez, Francisco José; Goirigolzarri Artaza, Josebe; Castedo Mejuto, Evaristo; Burgos Lázaro, Raúl; García Montero, Carlos; Moñivas Palomero, Vanessa; Mingo Santos, Susana; González Román, Ana Isabel; Álvarez Avelló, José Manuel; Vidal Fernández, Mercedes; Forteza Gil, Alberto; Alonso-Pulpón, Luis

2017-09-01

Most long-term ventricular assist devices (VADs) that are currently implanted are intracorporeal continuous-flow devices. Their main limitations include their high cost and inability to provide biventricular support. The aim of this study was to describe the results of using paracorporeal pulsatile-flow VADs as a bridge to transplant (BTT) in adult patients. Retrospective analysis of the characteristics, complications, and outcomes of a single-center case series of consecutive patients treated with the EXCOR VAD as BTT between 2009 and 2015. During the study period, 25 VADs were implanted, 6 of them biventricular. Ventricular assist devices were indicated directly as a BTT in 12 patients and as a bridge to decision in 13 due to the presence of potentially reversible contraindications or chance of heart function recovery. Twenty patients (80%) were successfully bridged to heart transplant after a median of 112 days (range, 8-239). The main complications included infectious (52% of patients), neurological events (32%, half of them fatal), bleeding (28%), and VAD malfunction requiring component replacement (28%). Eighty percent of patients with the EXCOR VAD as BTT achieved the goal after an average of almost 4 months of support. The most frequent complications were infectious, and the most severe were neurological. In our enivonment, the use of these pulsatile-flow VAD as BTT is a feasible strategy that obtains similar outcomes to those of intracorporeal continuous-flow devices. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure

DEFF Research Database (Denmark)

Petersen, L J; Petersen, J R; Talleruphuus, U

1997-01-01

The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. The aim...... of the present study was to evaluate the potential relationship between these indices and the rate of decline in renal function, as reflected by changes in different parameters of renal function in patients with chronic renal failure....

The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic renal failure

DEFF Research Database (Denmark)

Petersen, L J; Petersen, J R; Ladefoged, S D

1995-01-01

The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurement of downstream renal artery resistance. Little information is available on their value in chronic renal failure and their correlation to parameters of renal function and haemodynamics. The aim...... was to compare PI and RI of renal arteries in healthy volunteers and in patients with hypertension and chronic renal failure, and furthermore to study the correlation of these indices to measurements of renal haemodynamics and function by standard methods in patients with renal failure and hypertension....

GnRH在性成熟高白鲑神经系统及性腺中的分布定位%An Immunocytochemical Localization of GnRH in the Nerve System and Gonad of Mature Coregonus peled

Institute of Scientific and Technical Information of China (English)

曹玉洁; 贾斌; 柳建新; 李志远; 张莉

2011-01-01

摘要：应用免疫组织化学方法，系统观察性成熟期高白鲑(Coregonus peled)神经系统及性腺中的促性腺激素释放激素( GnRH)的分布情况。结果表明，GnRH在大脑、小脑、中脑、脊髓、延髓中免疫阳性反应明显，且主要分布在神经元内。GnRH免疫阳性细胞在卵巢和精巢中均有分布，而且其阳性部位在卵巢主要分布于小生长期卵母细胞；在精巢中主要分布于间质细胞和精原细胞中。本文讨论了GnRH直接或间接参与高白鲑性腺发育成熟调节的可能性。%Immunocytochemical staining technique was used to study the expression of gonadotropin-releasing hormone (GnRH) in the nervous system and gonad of Coregonus peled. The results showed that there were GnRH immunoreactive endocrine cells in the cerebrum,cerebellum,diencephalon,medulla oblongata,and spinal cord. There were GnRH immunoreactive endocrine cells in the ovary and testis. The positive staining was observed mainly in the small growing oocyte, and in the interstitial cells and spermatogonia. The possible physiological function and morphological evidence of GnRH regulation on the development of gonad in C. Peled were discussed.

The carboxy-terminal tail or the intracellular loop 3 is required for β-arrestin-dependent internalization of a mammalian type II GnRH receptor.

Science.gov (United States)

Madziva, Michael T; Mkhize, Nonhlanhla N; Flanagan, Colleen A; Katz, Arieh A

2015-08-15

The type II GnRH receptor (GnRH-R2) in contrast to mammalian type I GnRH receptor (GnRH-R1) has a cytosolic carboxy-terminal tail. We investigated the role of β-arrestin 1 in GnRH-R2-mediated signalling and mapped the regions in GnRH-R2 required for recruitment of β-arrestin, employing internalization assays. We show that GnRH-R2 activation of ERK is dependent on β-arrestin and protein kinase C. Appending the tail of GnRH-R2 to GnRH-R1 enabled GRK- and β-arrestin-dependent internalization of the chimaeric receptor. Surprisingly, carboxy-terminally truncated GnRH-R2 retained β-arrestin and GRK-dependent internalization, suggesting that β-arrestin interacts with additional elements of GnRH-R2. Mutating serine and threonine or basic residues of intracellular loop 3 did not abolish β-arrestin 1-dependent internalization but a receptor lacking these basic residues and the carboxy-terminus showed no β-arrestin 1-dependent internalization. Our results suggest that basic residues at the amino-terminal end of intracellular loop 3 or the carboxy-terminal tail are required for β-arrestin dependent internalization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CT evaluation of sigmoid plate dehiscence causing pulsatile tinnitus

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Zhao, Pengfei; Lv, Han; Dong, Cheng; Wang, Zhenchang [Capital Medical University, Department of Radiology, Beijing Friendship Hospital, Beijing (China); Niu, Yantao; Xian, Junfang [Capital Medical University, Department of Radiology, Beijing Tongren Hospital, Beijing (China)

2016-01-15

To evaluate the characteristics of sigmoid plate dehiscence (SPD) causing pulsatile tinnitus (PT) on CT arteriography and venography (CTA + V). Thirty PT patients treated successfully with SPD reconstruction were enrolled. Sixty asymptomatic patients were matched. The location, extent, number of SPD cases and concomitant signs, including venous outflow dominance, transverse sinus stenosis, high jugular bulb, temporal bone pneumatization, height of pituitary gland and pituitary fossa, abnormal mastoid emissary vein, were detected and compared using CTA + V. More than one SPD was found on the symptomatic side in 13/30 PT patients (43.3 %). The upper segment of the sigmoid plate was involved in 29/44 SPDs in the vertical direction (65.9 %); the lateral wall was involved in 38/44 SPDs in the horizontal direction (86.4 %). Singular SPD was detected in 3/60 asymptomatic patients (1.67 ± 0.35 mm{sup 2}), less so in PT patients (7.97 ± 5.17 mm{sup 2}). Compared with the control group, ipsilateral venous outflow dominance, high jugular bulb and bilateral transverse sinus stenosis were more common in the PT group, together with deeper pituitary fossa and flatter pituitary glands. SPD causing PT has characteristic CT findings. It may be generated by vascular or intracranial pressure abnormalities and act as a common key to triggering PT's perception. (orig.)

CT evaluation of sigmoid plate dehiscence causing pulsatile tinnitus

International Nuclear Information System (INIS)

Zhao, Pengfei; Lv, Han; Dong, Cheng; Wang, Zhenchang; Niu, Yantao; Xian, Junfang

2016-01-01

To evaluate the characteristics of sigmoid plate dehiscence (SPD) causing pulsatile tinnitus (PT) on CT arteriography and venography (CTA + V). Thirty PT patients treated successfully with SPD reconstruction were enrolled. Sixty asymptomatic patients were matched. The location, extent, number of SPD cases and concomitant signs, including venous outflow dominance, transverse sinus stenosis, high jugular bulb, temporal bone pneumatization, height of pituitary gland and pituitary fossa, abnormal mastoid emissary vein, were detected and compared using CTA + V. More than one SPD was found on the symptomatic side in 13/30 PT patients (43.3 %). The upper segment of the sigmoid plate was involved in 29/44 SPDs in the vertical direction (65.9 %); the lateral wall was involved in 38/44 SPDs in the horizontal direction (86.4 %). Singular SPD was detected in 3/60 asymptomatic patients (1.67 ± 0.35 mm 2 ), less so in PT patients (7.97 ± 5.17 mm 2 ). Compared with the control group, ipsilateral venous outflow dominance, high jugular bulb and bilateral transverse sinus stenosis were more common in the PT group, together with deeper pituitary fossa and flatter pituitary glands. SPD causing PT has characteristic CT findings. It may be generated by vascular or intracranial pressure abnormalities and act as a common key to triggering PT's perception. (orig.)

Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

Science.gov (United States)

Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

2017-02-10

The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance.

Science.gov (United States)

Buff, P R; Messer, N T; Cogswell, A M; Johnson, P J; Keisler, D H; Ganjam, V K

2007-11-01

The objective of this study was to determine if seasonal and/or pulsatile variations occur in plasma concentrations of thyrotropin (TSH) and leptin in mares while maintaining a constant energy balance. Blood samples were collected every 20 min during a 24h period in winter and again in summer from six Quarter Horse type mares. Plasma concentrations of TSH, leptin, and T(4) were determined by radioimmunoassay. No differences were observed in body weight between winter (388.1+/-12.5 kg) and summer (406.2+/-12.5 kg; P=0.11). Plasma concentrations of TSH were greater in the summer (2.80+/-0.07 ng/ml) when compared to winter (0.97+/-0.07 ng/ml; P<0.001). Pulse frequency of TSH was not different between winter (6.17+/-0.78 pulses/24h) and summer (5.33+/-0.78 pulses/24h; P=0.49). Mean TSH pulse amplitude, pulse area, and area under the curve were all greater in summer compared to winter (3.11+/-0.10 ng/ml versus 1.20+/-0.10 ng/ml, 24.86+/-0.10 ng/ml min versus 13.46+/-1.90 ng/ml min, 3936+/-72.93 ng/ml versus 1284+/-72.93 ng/ml, respectively; P<0.01). Mean concentrations of leptin were greater in summer (2.48+/-0.17 ng/ml) compared to winter (0.65+/-0.17 ng/ml; P<0.001). Pulsatile secretion patterns of leptin were not observed in any horses during experimentation. Mean concentrations of T(4) were greater in winter (20.3+/-0.4 ng/ml) compared to summer (18.2+/-0.4 ng/ml; P<0.001). These seasonal differences between winter and summer provide evidence of possible seasonal regulation of TSH and leptin.

Low-dose prospectively electrocardiogram-gated axial dual-source CT angiography in patients with pulsatile bilateral bidirectional Glenn Shunt: an alternative noninvasive method for postoperative morphological estimation.

Directory of Open Access Journals (Sweden)

Xiaopeng Ji

Full Text Available To explore the clinical value of low-dose prospectively electrocardiogram-gated axial dual-source CT angiography (low-dose PGA scanning, CTA in patients with pulsatile bilateral bidirectional Glenn shunt (bBDG as an alternative noninvasive method for postoperative morphological estimation.Twenty patients with pulsatile bBDG (mean age 4.2±1.6 years underwent both low-dose PGA scanning and conventional cardiac angiography (CCA for the morphological changes. The morphological evaluation included the anatomy of superior vena cava (SVC and pulmonary artery (PA, the anastomotic location, thrombosis, aorto-pulmonary collateral circulation, pulmonary arteriovenous malformations, etc. Objective and subjective image quality was assessed. Bland-Altman analysis and linear regression analyses were used to evaluate the correlation on measurements between CTA and CCA. Effective radiation dose of both modalities was calculated.The CT attenuation value of bilateral SVC and PA was higher than 300 HU. The average subjective image quality score was 4.05±0.69. The morphology of bilateral SVC and PA was displayed completely and intuitively by CTA images. There were 24 SVC above PA and 15 SVC beside PA. Thrombosis was found in 1 patient. Collateral vessels were detected in 13 patients. No pulmonary arteriovenous malformation was found in our study. A strong correlation (R2>0.8, P0.The mean effective dose of CTA and CCA was 0.50±0.17 mSv and 4.85±1.34 mSv respectively.CT angiography with a low-dose PGA scanning is an accurate and reliable noninvasive examination in the assessment of morphological changes in patients with pulsatile bBDG.

Impacto do uso de anÃlogos de GnRH sobre o tecido e metabolismo Ãsseo de pacientes endometrÃoticas

OpenAIRE

Danyelle Craveiro de Aquino

2005-01-01

Este trabalho tem por objetivo avaliar mulheres portadoras de endometriose em uso de anÃlogos de GnRH investigando o metabolismo Ãsseo e massa Ãssea atravÃs da dosagem de marcadores sÃricos e realizaÃÃo de ultra-sonometria do calcÃneo, respectivamente. Trata-se de estudo observacional transversal tipo caso â controle prospectivo. Foi desenvolvido na Maternidade-Escola Assis Chateaubriand (MEAC) â UFC. Foram avaliadas 99 mulheres, divididas em 3 grupos, sendo 32 portadoras de endometriose diag...

Extrinsic nerves are not involved in branchial 5-HT dynamics or pulsatile urea excretion in Gulf toadfish, Opsanus beta.

Science.gov (United States)

Cartolano, Maria C; Amador, Molly H B; Tzaneva, Velislava; Milsom, William K; McDonald, M Danielle

2017-12-01

Gulf toadfish (Opsanus beta) can switch from continuously excreting ammonia as their primary nitrogenous waste to excreting predominantly urea in distinct pulses. Previous studies have shown that the neurotransmitter serotonin (5-HT) is involved in controlling this process, but it is unknown if 5-HT availability is under central nervous control or if the 5-HT signal originates from a peripheral source. Following up on a previous study, cranial nerves IX (glossopharyngeal) and X (vagus) were sectioned to further characterize their role in controlling pulsatile urea excretion and 5-HT release within the gill. In contrast to an earlier study, nerve sectioning did not result in a change in urea pulse frequency. Total urea excretion, average pulse size, total nitrogen excretion, and percent ureotely were reduced the first day post-surgery in nerve-sectioned fish but recovered by 72h post-surgery. Nerve sectioning also had no effect on toadfish urea transporter (tUT), 5-HT transporter (SERT), or 5-HT 2A receptor mRNA expression or 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) abundance in the gill, all of which were found consistently across the three gill arches except 5-HIAA, which was undetectable in the first gill arch. Our findings indicate that the central nervous system does not directly control pulsatile urea excretion or local changes in gill 5-HT and 5-HIAA abundance. Copyright © 2017 Elsevier Inc. All rights reserved.

Uso de antagonista de GnRH (cetrorelix em dose única para evitar ovulações prematuras em ciclos de fertilização assistida Single dose of GnRH antagonist (cetrorelix to avoid premature ovulation in assisted fertilization cycles

Directory of Open Access Journals (Sweden)

Pedro Luís Rosan

2003-09-01

Full Text Available OBJETIVO: verificar a eficácia de uma dose única subcutânea de acetato de cetrorelix em evitar a ovulação prematura em ciclos de fertilização assistida. MÉTODOS: estudo prospectivo, randomizado e controlado, pelo qual foram avaliados 20 ciclos de estimulação ovariana em mulheres submetidas a fertilização assistida, 10 das quais utilizaram o esquema tradicional de bloqueio hipofisário com análogos de GnRH em doses diárias (grupo controle e 10 utilizaram antagonista de GnRH em dose única de 3 mg no 7º dia de estimulação ovariana (grupo cetrorelix. Foram dosados FSH, LH, estradiol e progesterona no soro no primeiro e sétimo dia da estimulação, no dia da injeção de HCG e no dia da captação de oócitos. Os grupos foram comparados entre si quanto a eficácia do bloqueio hipofisário (nível de progesterona no dia da aplicação do HCG e desempenho nos ciclos de fertilização assistida (ampolas de gonadotrofinas utilizadas, folículos maiores que 18 mm, oócitos captados, taxas de fertilização, implantação e gravidez utilizando os testes de Mann-Whitney e exato de Fisher. RESULTADOS: não houve diferença significativa entre os grupos controle e cetrorelix, respectivamente, para a mediana da idade (31,5 e 34 anos, índice de massa corpórea (24 e 22, ampolas de gonadotrofinas utilizadas (34 e 32, folículos recrutados (3,5 e 3,0, oócitos captados (11 e 5, embriões obtidos (4 e 3, taxas de fertilização (93,7 e 60%, p = 0,07 e gravidez (50 e 60%, p = 0,7. Em ambos os grupos observou-se bloqueio hipofisário eficaz durante o período de estimulação ovariana. CONCLUSÕES: estes resultados confirmam a eficácia da dose única de 3 mg de acetato de cetrorelix em prevenir ovulações prematuras em pacientes submetidas a fertilização assistida, mostrando tendência a obtenção de menor número de embriões e menores taxas de fertilização no grupo cetrorelix em relação ao grupo controle. As taxas de implantação e

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes

DEFF Research Database (Denmark)

Aksglaede, L.; Jensen, Rikke Bodin Beck; Carlsen, E.

2008-01-01

testicular failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study. METHODS: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive...... basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone...

The chicken type III GnRH receptor homologue is predominantly expressed in the pituitary, and exhibits similar ligand selectivity to the type I receptor

Science.gov (United States)

Joseph, Nerine T; Morgan, Kevin; Sellar, Robin; McBride, Derek; Millar, Robert P; Dunn, Ian C

2009-01-01

Two GnRH isoforms (cGnRH-I and GnRH-II) and two GnRH receptor subtypes (cGnRH-R-I and cGnRH-R-III) occur in chickens. Differential roles for these molecules in regulating gonadotrophin secretion or other functions are unclear. To investigate this we cloned cGnRH-R-III from a broiler chicken and compared its structure, expression and pharmacological properties with cGnRH-R-I. The broiler cGnRH-R-III cDNA was 100% identical to the sequence reported in the red jungle fowl and white leghorn breed. Pituitary cGnRH-R-III mRNA was ∼1400-fold more abundant than cGnRH-R-I mRNA. Northern analysis indicated a single cGnRH-R-III transcript. A pronounced sex and age difference existed, with higher pituitary transcript levels in sexually mature females versus juvenile females. In contrast, higher expression levels occurred in juvenile males versus sexually mature males. Functional studies in COS-7 cells indicated that cGnRH-R-III has a higher binding affinity for GnRH-II than cGnRH-I (Kd: 0·57 vs 19·8 nM) with more potent stimulation of inositol phosphate production (ED50: 0·8 vs 4·38 nM). Similar results were found for cGnRH-R-I, (Kd: 0·51 vs 10·8 nM) and (ED50: 0·7 vs 2·8 nM). The initial rate of internalisation was faster for cGnRH-R-III than cGnRH-R-I (26 vs 15·8%/min). Effects of GnRH antagonists were compared at the two receptors. Antagonist #27 distinguished between cGnRH-R-I and cGnRH-R-III (IC50: 2·3 vs 351 nM). These results suggest that cGnRH-R-III is probably the major mediator of pituitary gonadotroph function, that antagonist #27 may allow delineation of receptor subtype function in vitro and in vivo and that tissue-specific recruitment of cGnRH-R isoforms has occurred during evolution. PMID:19380456

Behavior of feral horses in response to culling and GnRH immunocontraception

Science.gov (United States)

Ransom, Jason I.; Powers, Jenny G.; Garbe, Heidi M.; Oehler, Michael W.; Nett, Terry M.; Baker, Dan L.

2014-01-01

Wildlife management actions can alter fundamental behaviors of individuals and groups,which may directly impact their life history parameters in unforeseen ways. This is especially true for highly social animals because changes in one individual’s behavior can cascade throughout its social network. When resources to support populations of social animals are limited and populations become locally overabundant, managers are faced with the daunting challenge of decreasing population size without disrupting core behavioral processes. Increasingly, managers are turning to fertility control technologies to supplement culling in efforts to suppress population growth, but little is quantitatively known about how either of these management tools affects behavior. Gonadotropin releasing hormone (GnRH) is a small neuropeptide that performs an obligatory role in mammalian reproduction and has been formulated into the immunocontraceptive GonaCon-BTM. We investigated the influences of this vaccine on behavior of feral horses (Equus caballus) at Theodore Roosevelt National Park, North Dakota, USA, for a year preceding and a year following nonlethal culling and GnRH-vaccine treatment. We observed horses during the breeding season and found only minimal differences in time budget behaviors of free-ranging female feral horses treated with GnRH and those treated with saline. The differences observed were consistent with the metabolic demands of pregnancy and lactation. We observed similar social behaviors between treatment groups, reflecting limited reproductive behavior among control females due to high rates of pregnancy and suppressed reproductive behavior among treated females due to GnRH-inhibited ovarian activity. In the treatment year, band stallion age was the only supported factor influencing herding behavior (P < 0.001), harem-tending behavior (P < 0.001), and agonistic behavior (P = 0.02). There was no difference between the mean body condition of control females (4

Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

DEFF Research Database (Denmark)

Sehested, A; Andersson, A M; Müller, J

2000-01-01

both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation......Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

Observation of the CSF pulsatile flow on MRI, (2)

International Nuclear Information System (INIS)

Ohara, Shigeki; Nagai, Hajime; Suzuka, Tomonao; Matsumoto, Takashi; Banno, Tatsuo

1988-01-01

In a retrospective study of the MR images of 289 neurosurgical patients, a loss of the signal intensity (the signal-void phenomenon =SVP) of the cerebrospinal fluid in the mesencephalic aqueduct was observed in 77 patients. The CSF in the cranial cavity flows toward the spinal sac in a to-and-fro manner in response to the pulsations of the brain. Because the intracranial compliance is lower than the intraspinal compliance, the systolic expansions and diastolic reductions in the brain volume are buffered by the spinal cavity via this to-and-fro flow of CSF. The SVP reflects the CSF pulsatile flow forced out of the intracranial space into the intraspinal space by the brain's pulsations. Intracranial abnormalities can be divided into two categories according to the craniospinal compliance (CC): normal CC (communicating hydrocephalus) and decreased CC (supratentorial tumor). We may expect those conditions which increase compliance to increase the CSF flow and yield a more prominent SVP. Conversely, conditions which decrease compliance may be expected to decrease the flow and extinguish the SVP. Both the brain's pulsations and the compliance of the craniospinal cavity are closely related to the presence of the SVP in CSF, as revealed by MRI. The SVP in CSF may reflect the pressure-buffering capacity of the cranio-spinal cavity. If further investigation supports our hypothesis, it may be possible to estimate the intracranial pressure noninvasively. (author)

Cerebrovascular pulsatility in patients with sleep-disordered breathing.

Science.gov (United States)

Ramos, Alberto R; Cabral, Digna; Lee, David J; Sacco, Ralph L; Rundek, Tatjana

2013-05-01

The aim of our study is to determine the association between the pulsatility index (PI), a surrogate of cerebral small vessel disease and sleep-disordered breathing (SDB). We conducted a transcranial Doppler ultrasound (TCD) study of 19 consecutive patients free of stroke and cardiovascular disease, referred for the evaluation of SDB. TCD was performed by a certified technologist. Subsequent polysomnography was performed according to the practice parameters of the American Academy of Sleep Medicine. We evaluated the association between the apnea-hypopnea index (AHI), the oxygen nadir, the blood flow velocities, and the Gosling PI, for the middle cerebral artery. We performed Spearman's rank correlation and nonparametric regression to evaluate the relationship between AHI, oxygen levels, and the PI. Median age was 48 years (range 37-83), with 52 % male sex (n = 10), and median BMI of 29.9 (range 25-40.4). The median AHI was 16.4 (0.2-69). The median PI was 0.97 (0.72-1.89) cm/s. The PI correlated with the AHI (rho = 0.44; p = 0.004) and with age (rho = 0.57; p = 0.001). Nonparametric regression adjusting for age showed a positive association between the AHI and the PI (standardized estimate = 0.88; p = 0.002). There was no relation between the oxygen nadir and the PI. We observed increased PI in patients with SDB during wakefulness. The PI could potentially be an estimate of cerebral small vessel disease in patients with SDB and hence allow evaluating cerebral hemodynamics during wakefulness with a clinically relevant device.

Transition to turbulence in pulsatile flow through heart valves--a modified stability approach.

Science.gov (United States)

Bluestein, D; Einav, S

1994-11-01

The presence of turbulence in the cardiovascular system is generally an indication of some type of abnormality. Most cardiologists agree that turbulence near a valve indicates either valvular stenosis or regurgitation, depending on the phase of its occurrence during the cardiac cycle. As no satisfying analytical solutions of the stability of turbulent pulsatile flow exist, accurate, unbiased flow stability criteria are needed for the identification of turbulence initiation. The traditional approach uses a stability diagram based upon the stability of a plane Stokes layer where alpha (the Womersley parameter) is defined by the fundamental heart rate. We suggest a modified approach that involves the decomposition of alpha into its frequency components, where alpha is derived from the preferred modes induced on the flow by interaction between flow pulsation and the valve. Transition to turbulence in pulsatile flow through heart values was investigated in a pulse duplicator system using three polymer aortic valve models representing a normal aortic valve, a 65 percent stenosed valve and a 90 percent severely stenosed valve, and two mitral valve models representing a normal mitral valve and a 65 percent stenosed valve. Valve characteristics were closely simulated as to mimic the conditions that alter flow stability and initiate turbulent flow conditions. Valvular velocity waveforms were measured by laser Doppler anemometry (LDA). Spectral analysis was performed on velocity signals at selected spatial and temporal points to produce the power density spectra, in which the preferred frequency modes were identified. The spectra obtained during the rapid closure stage of the valves were found to be governed by the stenosis geometry. A shift toward higher dominant frequencies was correlated with the severity of the stenosis. According to the modified approach, stability of the flow is represented by a cluster of points, each corresponding to a specific dominant mode apparent

Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

Science.gov (United States)

Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

2011-01-01

Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pulsatile flow effects on the hemodynamics of intracranial aneurysms.

Science.gov (United States)

Le, Trung B; Borazjani, Iman; Sotiropoulos, Fotis

2010-11-01

High-resolution numerical simulations are carried out to systematically investigate the effect of the incoming flow waveform on the hemodynamics and wall shear stress patterns of an anatomic sidewall intracranial aneurysm model. Various wave forms are constructed by appropriately scaling a typical human waveform such that the waveform maximum and time-averaged Reynolds numbers, the Womersley number (α), and the pulsatility index (PI) are systematically varied within the human physiologic range. We show that the waveform PI is the key parameter that governs the vortex dynamics across the aneurysm neck and the flow patterns within the dome. At low PI, the flow in the dome is similar to a driven cavity flow and is characterized by a quasi-stationary shear layer that delineates the parent artery flow from the recirculating flow within the dome. At high PI, on the other hand, the flow is dominated by vortex ring formation, transport across the neck, and impingement and breakdown at the distal wall of the aneurysm dome. We further show that the spatial and temporal characteristics of the wall shear stress field on the aneurysm dome are strongly correlated with the vortex dynamics across the neck. We finally argue that the ratio between the characteristic time scale of transport by the mean flow across the neck and the time scale of vortex ring formation can be used to predict for a given sidewall aneurysm model the critical value of the waveform PI for which the hemodynamics will transition from the cavity mode to the vortex ring mode.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

Science.gov (United States)

Tremblay, Jan-Alexis; Beaubien-Souligny, William; Elmi-Sarabi, Mahsa; Desjardins, Georges; Denault, André Y

2017-10-15

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

Science.gov (United States)

Dufourny, Laurence; Lomet, Didier

2017-12-01

Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

Science.gov (United States)

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of

PIV Measurement of Pulsatile Flows in 3D Curved Tubes Using Refractive Index Matching Method

Energy Technology Data Exchange (ETDEWEB)

Hong, Hyeon Ji; Ji, Ho Seong; Kim, Kyung Chun [Pusan Nat’l Univ., Busan (Korea, Republic of)

2016-08-15

Three-dimensional models of stenosis blood vessels were prepared using a 3D printer. The models included a straight pipe with axisymmetric stenosis and a pipe that was bent 10° from the center of stenosis. A refractive index matching method was utilized to measure accurate velocity fields inside the 3D tubes. Three different pulsatile flows were generated and controlled by changing the rotational speed frequency of the peristaltic pump. Unsteady velocity fields were measured by a time-resolved particle image velocimetry method. Periodic shedding of vortices occurred and moves depended on the maximum velocity region. The sizes and the positions of the vortices and symmetry are influenced by mean Reynolds number and tube geometry. In the case of the bent pipe, a recirculation zone observed at the post-stenosis could explain the possibility of blood clot formation and blood clot adhesion in view of hemodynamics.

PIV Measurement of Pulsatile Flows in 3D Curved Tubes Using Refractive Index Matching Method

International Nuclear Information System (INIS)

Hong, Hyeon Ji; Ji, Ho Seong; Kim, Kyung Chun

2016-01-01

Three-dimensional models of stenosis blood vessels were prepared using a 3D printer. The models included a straight pipe with axisymmetric stenosis and a pipe that was bent 10° from the center of stenosis. A refractive index matching method was utilized to measure accurate velocity fields inside the 3D tubes. Three different pulsatile flows were generated and controlled by changing the rotational speed frequency of the peristaltic pump. Unsteady velocity fields were measured by a time-resolved particle image velocimetry method. Periodic shedding of vortices occurred and moves depended on the maximum velocity region. The sizes and the positions of the vortices and symmetry are influenced by mean Reynolds number and tube geometry. In the case of the bent pipe, a recirculation zone observed at the post-stenosis could explain the possibility of blood clot formation and blood clot adhesion in view of hemodynamics.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women

OpenAIRE

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-01-01

Objective To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. Materials/methods A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH + hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III...

Evaluation of pulsatility index and diameter of the jugular vein and superficial body temperature as physiological indices of temperament in weaned beef calves: relationship with serum cortisol concentrations, rectal temp..

Science.gov (United States)

The relationship between temperament, pulsatility index and diameter of the jugular vein, and body temperature was assessed in Angus crossbred calves (262±24.9 days old). Temperament scores were used to classify calves as calm (n=31), intermediate (n=32), or temperamental (n=28). Blood samples were ...

Um sistema de ventrículo pulmonar produzindo pressão pulsátil em único ventrículo: modelo experimental A pulmonary ventricle system producing pulsatile pressure in single ventricle: experimental model

Directory of Open Access Journals (Sweden)

Bilgein Emrecan

2006-09-01

Full Text Available OBJETIVO: Pacientes com ventrículo único funcional têm prognóstico ruim, que resulta em insuficiência cardíaca, mesmo após tratamento cirúrgico. As operações derivação cavo-pulmonar (exceto pelas conexões do átrio direito ao ventrículo direito não apresentam sistema ventricular pulmonar com pressão pulsátil, além do fluxo reduzido ao ventrículo único. Para resolver o problema, tentamos criar um ventrículo pulmonar que produza pressão pulsátil experimentalmente. MÉTODO: Tentamos criar um sistema ventricular direito que produzisse pressão pulsátil. O modelo experimental foi realizado em seis ovelhas. As pressões do ventrículo pulmonar criado, da artéria pulmonar e do ventrículo esquerdo foram medidas após a saída da circulação extracorpórea. RESULTADOS: A média das pressões arteriais pulmonares sistólica e diastólica foi 15,6 ± 2,0 mmHg e 4,5 ± 1,5 mmHg. A média da pressão sistólica ventricular esquerda foi 76,6 ± 4,4 mmHg. CONCLUSÃO: Um ventrículo que produza pressão pulsátil é necessário para a regulação do fluxo da artéria pulmonar, com pressão venosa central e pressão pulmonar não pulsátil nas anomalias como ventrículos únicos funcionais.OBJECTIVE: Patients with functional single ventricle show bad survey, most of which result in cardiac failure even in the case that they are operated. The right heart bypass operations except for right atrium and right ventricle connections lack pulsatile pulmonary ventricle system besides the volume lack coming to the common ventricle. To solve the problem, we tried to create a pulmonary ventricle which produces pulsatile pressure experimentally. METHODS: We tried to form a right ventricle system which produces pulsatile pressure. The experimental model was carried on six sheep. The pressures of the created pulmonary ventricle, pulmonary artery and the left ventricle were measured after leaving the cardiopulmonary bypass. RESULTS: The mean of the

Numerical investigation of flow parameters for solid rigid spheroidal particle in a pulsatile pipe flow

Science.gov (United States)

Varghese, Joffin; Jayakumar, J. S.

2017-09-01

Quantifying, forecasting and analysing the displacement rates of suspended particles are essential while discussing about blood flow analysis. Because blood is one of the major organs in the body, which enables transport phenomena, comprising of numerous blood cells. In order to model the blood flow, a flow domain was created and numerically simulated. Flow field velocity in the stream is solved utilizing Finite Volume Method utilizing FVM unstructured solver. In pulsatile flow, the effect of parameters such as average Reynolds number, tube radius, particle size and Womersley number are taken into account. In this study spheroidal particle trajectory in axial direction is simulated at different values of pulsating frequency including 1.2 Hz, 3.33 Hz and 4.00 Hz and various densities including 1005 kg/m3 and 1025 kg/m3 for the flow domain. The analysis accomplishes the interaction study of blood constituents for different flow situations which have applications in diagnosis and treatment of cardio vascular related diseases.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

Science.gov (United States)

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the

Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

Science.gov (United States)

Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

1983-04-01

Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

A study of the pulsatile flow and its interaction with rectangular leaflets

Science.gov (United States)

Ledesma, Rene; Zenit, Roberto; Pulos, Guillermo

2009-11-01

To avoid the complexity and limited understanding of the 3D pulsatile flow field through heart valves, a cardiac-like flow circuit and a test channel were designed to study the behavior of bidimensional leaflets made of hyperelastic materials. We study a simple 2D arrangement to understand the basic physics of the flow-leaflet interaction. Creating a periodic pressure gradient, measurements of leaflet deflection were obtained for different flow conditions, geometries and materials. Using PIV and Phase Locking techniques, we have obtained the leaflet motion and the time-dependent flow velocity fields. The results show that two dimensionless parameters determine the performance of a simple bi-dimensional valve, in accordance with the flow conditions applied: π1=f(sw)^1/2(E/ρ)^1/2 and π2=V/(2slw), where f is the pulsation frequency, V is the stroke volume, s, w and l are the dimensions on the leaftlet and E and ρ are the elastic modulus and density of the material, respectively. Furthermore, we have identified the conditions for which the fluid stresses can be minimized. With these results we propose a new set of parameters to improve the performance of prosthetic heart valves and, in consequence, to reduce blood damage.

A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

Directory of Open Access Journals (Sweden)

Günther Eissner

2011-07-01

Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

Pulsatile pressure driven rarefied gas flow in long rectangular ducts

Science.gov (United States)

Tsimpoukis, Alexandros; Valougeorgis, Dimitris

2018-04-01

The pulsatile pressure driven fully developed flow of a rarefied gas through an orthogonal duct is investigated, based on the time-dependent linear Bhatnagar, Gross, and Krook equation, by decomposing the flow into its steady and oscillatory parts. The investigation is focused on the oscillatory part, which is characterized by the gas rarefaction and oscillation parameters, the duct aspect ratio, and the accommodation coefficient. As the oscillation frequency is increased, the amplitude of all macroscopic quantities is decreased, while their phase angle lag is increased reaching the limiting value of π/2. As the gas becomes more rarefied, higher frequencies are needed to trigger this behavior. At small and moderate frequencies, there is a critical degree of gas rarefaction, where a maximum flow rate is obtained. As the duct aspect ratio is decreased and tends to zero, the flow rate and mean wall shear stress amplitudes are increased, while their phase angle lags are slightly affected. The accommodation coefficient has a significant effect on the amplitude and a very weak one on the phase angle of the macroscopic quantities. The computation of the inertia and viscous forces clarifies when the flow consists of only one oscillating viscous region or of two regions, namely, the inviscid piston flow in the core and the oscillating Stokes layer at the wall with the velocity overshooting. Finally, the time average oscillatory pumping power is increased as the oscillation frequency is reduced and its maximum value is one half of the corresponding steady one.

Fiscal 2000 achievement report on the research and development of medical and welfare apparatus/technology. Totally implantable artificial heart for clinical use; 2000 nendo iryo fukushi kiki gijutsu kenkyu kaihatsu seika hokokusho. Rinsho oyo ni muketa tainai umekomigata jinko shinzo system

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-05-01

In the development of control technologies for a pulsatile pump, studies proceeded with a view to using a mixed venous blood oxygen saturation sensor, an ultrasonic sensor, and an absolute pressure sensor. Efforts were started to downsize the hydraulic actuator and to enhance its efficiency. In the development of a non-pulsatile artificial heart, the GyroP1710 series of artificial heart systems of Japanese make was developed, which employed a curved inlet known to be highly compatible from the anatomical point of view. In the development of a total system, a pulsatile auxiliary artificial heart was given a chronic animal test which continued approximately three weeks, when it yielded a flow of approximately 4 liters/minute showing that it would be practical as an auxiliary heart. As for the non-pulsatile artificial heart, a cardiopulmonary bypass test was conducted, when the blood circulation behavior was normal and organ functions were sustained. The free hemoglobin level was 9.3mg/dl achieving the target value, and the test animal lived as long as 50 days. (NEDO)

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

DEFF Research Database (Denmark)

Juul, A; Scheike, Thomas Harder; Nielsen, C T

1995-01-01

between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P ...Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor.

Science.gov (United States)

Janovick, Jo Ann; Patny, Akshay; Mosley, Ralph; Goulet, Mark T; Altman, Michael D; Rush, Thomas S; Cornea, Anda; Conn, P Michael

2009-02-01

The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model for studying pharmacological chaperones (pharmacoperones), drugs that rescue misfolded and misrouted protein mutants and restore them to function. This technique forms the basis of a therapeutic approach of rescuing mutants associated with human disease and restoring them to function. The present study relies on computational modeling, followed by site-directed mutagenesis, assessment of ligand binding, effector activation, and confocal microscopy. Our results show that two different chemical classes of pharmacoperones act to stabilize hGnRHR mutants by bridging residues D(98) and K(121). This ligand-mediated bridge serves as a surrogate for a naturally occurring and highly conserved salt bridge (E(90)-K(121)) that stabilizes the relation between transmembranes 2 and 3, which is required for passage of the receptor through the cellular quality control system and to the plasma membrane. Our model was used to reveal important pharmacophoric features, and then identify a novel chemical ligand, which was able to rescue a D(98) mutant of the hGnRHR that could not be rescued as effectively by previously known pharmacoperones.

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

Energy Technology Data Exchange (ETDEWEB)

Lv, Han [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Neuroradiology Division, Department of Radiology, Stanford University, CA, 94305 (United States); Zhao, Pengfei [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Liu, Zhaohui [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Li, Rui; Zhang, Ling; Wang, Peng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Yan, Fei [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Liu, Liheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Guopeng; Zeng, Rong [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Li, Ting [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Dong, Cheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Gong, Shusheng, E-mail: gongss@ccmu.edu.cn [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Zhenchang, E-mail: cjr.wzhch@vip.163.com [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China)

2016-11-15

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

International Nuclear Information System (INIS)

Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

2016-01-01

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

[Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

Science.gov (United States)

Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

2010-05-01

Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea.

Science.gov (United States)

Genazzani, Alessandro D; Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Santagni, Susanna; Rattighieri, Erica; Ricchieri, Federica; Chierchia, Elisa; Simoncini, Tommaso

2012-02-01

To evaluate the influence of estriol administration on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study. Patients with FHA in a clinical research environment. Twelve hypogonadotropic patients affected by FHA. Pulsatility study of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a gonadotropin-releasing hormone (GnRH) test (10 μg in bolus) at baseline condition and after 8 weeks of therapy with 2 mg/day of estriol. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17α-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A), testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. After treatment, the FHA patients showed a statistically significant increase of LH plasma levels (from 0.7 ± 0.1 mIU/mL to 3.5 ± 0.3 mIU/mL) and a statistically significant increase of LH pulse amplitude with no changes in LH pulse frequency. In addition, the LH response to the GnRH bolus was a statistically significant increase. Estriol administration induced the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion. These findings suggest that estriol administration modulates the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of LH synthesis and secretion in hypogonadotropic patients with FHA. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of the Aperio thrombectomy device when compared to the Solitaire AB/FR and the Revive devices in a pulsatile flow system.

Science.gov (United States)

Saleh, Mahdi; Spence, John Nathan; Nayak, Sanjeev; Pearce, Gillian; Tennuci, Christopher; Roffe, Christine

2012-01-01

There are a limited number of studies comparing the Aperio mechanical thrombectomy device to other stent-based devices. In this paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and Revive devices in a model of the middle cerebral artery (MCA) within a modified pulsatile flow system. Thrombi made of lamb's blood were placed into a pulsatile flow system perfused with Hartmann's solution at 80 bpm with a mean pressure of 90 mm Hg. 30 experiments were run with each device. Recanalization rates were similar for all three devices (90% with the Solitaire AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of attempts to retrieve the thrombus was also similar for all three devices (1.7 with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot fragmentation and embolization rates revealed no statistical significance but there was a trend towards lower embolization rates with the Aperio (23% compared to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the Solitaire AB, FR and 169 seconds for the Revive). In this in vitro setting, the Aperio device seems to be an efficacious and safe device when compared to other similar clinically used mechanical thrombectomy devices. Larger clinical trials are warranted.

Efecto del celo y el tratamiento con GnRH sobre la tasa de concepción en programas de inseminación artificial y transferencia de embriones bovinos

OpenAIRE

Vera Cedeño, Jofre Andrés

2017-01-01

Tesis (Maestría en Reporducción Bovina) -- UNC- Facultad de Ciencias Agropecuarias, 2017 Esta tesis tuvo como objetivo evaluar el efecto de la presentación de celos y el tratamiento con GnRH como segundo inductor de ovulación en los animales que no manifiestan celo, sobre la tasa de concepción (TC) a los programas de inseminación artificial (IATF) y de transferencia embrionaria a tiempo fijo (TETF). Se realizaron cuatro experimentos en vacas y vaquillonas de ...

Pulsatile Flow and Transport of Blood past a Cylinder: Basic Transport for an Artificial Lung.

Science.gov (United States)

Zierenberg, Jennifer R.

2005-11-01

The fluid mechanics and transport for flow of blood past a single cylinder is investigated using CFD. This work refers to an artificial lung in which oxygen travels through fibers oriented perpendicularly to the incoming blood flow. A pulsatile blood flow was considered: Ux=U0[ 1+A( φt ) ], where Ux is the velocity far from the cylinder. The Casson equation was used to describe the shear thinning and yield stress properties of blood. The presence of hemoglobin (i.e. facilitated diffusion) was considered. We examined the effect of A, U0 and φ on the flow and transport by varying the dimensionless parameters: A; Reynolds number, Re; and Womersley parameter, α. Two different feed gases were considered: pure O2 and air. The flow and concentration fields were computed for Re = 5, 10, and 40, 0 transport is found to primarily depend on Re and to increase with increasing Re, α and decreasing A. The presence of hemoglobin increases mass transport. Supported by NIH HL69420, NSF Fellowship

On the Evolution of Pulsatile Flow Subject to a Transverse Impulse Body Force

Science.gov (United States)

di Labbio, Giuseppe; Keshavarz-Motamed, Zahra; Kadem, Lyes

2014-11-01

In the event of an unexpected abrupt traffic stop or car accident, automotive passengers will experience an abrupt body deceleration. This may lead to tearing or dissection of the aortic wall known as Blunt Traumatic Aortic Rupture (BTAR). BTAR is the second leading cause of death in automotive accidents and, although quite frequent, the mechanisms leading to BTAR are still not clearly identified, particularly the contribution of the flow field. As such, this work is intended to provide a fundamental framework for the investigation of the flow contribution to BTAR. In this fundamental study, pulsatile flow in a three-dimensional, straight pipe of circular cross-section is subjected to a unidirectional, transverse, impulse body force applied on a strictly bounded volume of fluid. These models were simulated using the Computational Fluid Dynamics (CFD) software FLUENT. The evolution of fluid field characteristics was investigated during and after the application of the force. The application of the force significantly modified the flow field. The force induces a transverse pressure gradient causing the development of secondary flow structures that dissipate the energy added by the acceleration. Once the force ceases to act, these structures are carried downstream and gradually dissipate their excess energy.

Processing oscillatory signals by incoherent feedforward loops

Science.gov (United States)

Zhang, Carolyn; Wu, Feilun; Tsoi, Ryan; Shats, Igor; You, Lingchong

From the timing of amoeba development to the maintenance of stem cell pluripotency,many biological signaling pathways exhibit the ability to differentiate between pulsatile and sustained signals in the regulation of downstream gene expression.While networks underlying this signal decoding are diverse,many are built around a common motif, the incoherent feedforward loop (IFFL),where an input simultaneously activates an output and an inhibitor of the output.With appropriate parameters,this motif can generate temporal adaptation,where the system is desensitized to a sustained input.This property serves as the foundation for distinguishing signals with varying temporal profiles.Here,we use quantitative modeling to examine another property of IFFLs,the ability to process oscillatory signals.Our results indicate that the system's ability to translate pulsatile dynamics is limited by two constraints.The kinetics of IFFL components dictate the input range for which the network can decode pulsatile dynamics.In addition,a match between the network parameters and signal characteristics is required for optimal ``counting''.We elucidate one potential mechanism by which information processing occurs in natural networks with implications in the design of synthetic gene circuits for this purpose. This work was partially supported by the National Science Foundation Graduate Research Fellowship (CZ).

Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

Science.gov (United States)

Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

2015-01-01

The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p valsartan β cyclodextrin complex was significantly higher (p valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

Science.gov (United States)

Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

2017-03-01

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

Evaluation of the renal resistive index and pulsatility index in patients with pleural effusion by duplex Doppler ultrasonography.

Science.gov (United States)

Değirmenci, Nevbahar Akcar; Metintaş, Muzaffer; Atlanoglu, Sahinde; Yıldırım, Huseyin

2013-01-01

The aim of the study was to evaluate the renal resistive index (RI) and pulsatility index (PI) in patients with pleural effusion (PE). We studied the mean renal RI and PI in 50 patients with PE and 30 healthy volunteers by Doppler sonography. We grouped effusion as unilateral and bilateral. Statistical analysis was done by independent t test and correlation coefficient analysis. The mean RI/PI in healthy volunteers and in PE patients was 0.58/0.93 and 0.72/1.35, respectively. We observed a significantly higher RI and PI in patients when compared with healthy volunteers (all p effusion (0.74 or 1.55, respectively) (p > 0.05). Pleural effusion might result in increased renal impedance as seen in cirrhosis, which is a rather complicated pathophysiological process, without causing any morphological changes in kidneys.

Effect of resynchronization with GnRH or progesterone (P4) intravaginal device (CIDR) on Day 23 after timed artificial insemination on cumulative pregnancy and embryonic losses in CIDR-GnRH synchronized Nili-Ravi buffaloes.

Science.gov (United States)

Arshad, Usman; Qayyum, Arslan; Hassan, Mubbashar; Husnain, Ali; Sattar, Abdul; Ahmad, Nasim

2017-11-01

The objective of the present study was to determine the effect of resynchronization on Day 23 with either GnRH or P4 (controlled internal drug release device containing progesterone; CIDR) on pregnancy rate, cumulative pregnancy, and embryonic and fetal losses in CIDR-GnRH synchronized Nili-Ravi buffaloes. Buffaloes (n = 181) of mixed parity, lactating, 181 ± 73 days postpartum, a body condition score (BCS) of 3.2 ± 0.5 (scale of 1-5), and 450-600 kg weight were subjected to synchronization and resynchronization. All buffaloes received CIDR on Day -9.5. In addition, GnRH was injected 36 h after CIDR removal, and timed artificial insemination (TAI) was performed 18 h later (Day 0). On Day 23, buffaloes were randomly assigned to receive one of the following treatments: 1) CON (n = 63), 2) P4 (n = 55), and 3) GnRH (n = 63) for resynchronization (2nd AI). Pregnancy rate, and embryonic and fetal losses were monitored by serial ultrasonography on Days 30, 45, 60, and 90 after synchronization (1st TAI), respectively. The pregnancy rate in GnRH-treated buffaloes remained significantly and consistently higher (P  0.05) between the OVS and CIDR groups; whereas the, cumulative pregnancy rate in GnRH + OVS buffaloes (81%) after 1st and 2 nd AI when determined on Day 64 was higher (P losses were significantly lower (P losses were fewer and did not differ (P > 0.05) due to treatments on Day 60 or 90 post 1st AI. In conclusion, 1) the pregnancy rate and cumulative pregnancy rate in GnRH-treated buffaloes were higher than in CON buffaloes on Day 64 after synchronization and resynchronization, and 2) embryonic and fetal losses were lower in GnRH-treated buffaloes than in CON buffaloes when determined from Day 31-90 post 1st TAI. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

Science.gov (United States)

Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

2014-12-01

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

Gigantism due to growth hormone excess in a boy with optic glioma.

Science.gov (United States)

Drimmie, F M; MacLennan, A C; Nicoll, J A; Simpson, E; McNeill, E; Donaldson, M D

2000-10-01

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

[Which ovarian stimulation to which women: The polycystic ovary syndrome (PCOS)].

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Merviel, P; Bouée, S; Ménard, M; Le Martelot, M-T; Roche, S; Lelièvre, C; Chabaud, J-J; Jacq, C; Drapier, H; Beauvillard, D

2017-11-01

Polycystic ovarian syndrome (PCOS) is a frequent pathology in the young woman, linking infertility to a metabolic disease. Initial support will include a plan (in the case of overweight or obesity) to lose at least 5 to 10% of the weight. Subsequently, clomiphene citrate is the first treatment for ovulation induction with pregnancy rates of 40 to 80% after 6 cycles. If there is resistance to clomiphene citrate, the choice will be between the ovarian drilling (50-60% of pregnancy in the year following, including the half spontaneous) or ovarian stimulation with gonadotropins. The risk of ovarian stimulation in these women is hyperstimulation and multiple pregnancies. We also discuss the place of the GnRH pulsatile administration, insulin-sensitizers, in vitro fertilization and in vitro maturation in these women. Once infertility support, these women should be long-term followed because of the neoplasic and cardiovascular risks they present. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Investigation of pulsatile flowfield in healthy thoracic aorta models.

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Wen, Chih-Yung; Yang, An-Shik; Tseng, Li-Yu; Chai, Jyh-Wen

2010-02-01

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics plays a critical role in the development of aortic dissection and atherosclerosis, as well as many other diseases. Since fundamental fluid mechanics are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects, a joint experimental and numerical study was conducted in this study to determine the distributions of wall shear stress and pressure and oscillatory WSS index, and to examine their correlation with the aortic disorders, especially dissection. Experimentally, the Phase-Contrast Magnetic Resonance Imaging (PC-MRI) method was used to acquire the true geometry of a normal human thoracic aorta, which was readily converted into a transparent thoracic aorta model by the rapid prototyping (RP) technique. The thoracic aorta model was then used in the in vitro experiments and computations. Simulations were performed using the computational fluid dynamic (CFD) code ACE+((R)) to determine flow characteristics of the three-dimensional, pulsatile, incompressible, and Newtonian fluid in the thoracic aorta model. The unsteady boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured flowrate and pressure results during in vitro experiments. For the code validation, the predicted axial velocity reasonably agrees with the PC-MRI experimental data in the oblique sagittal plane of the thoracic aorta model. The thorough analyses of the thoracic aorta flow, WSSs, WSS index (OSI), and wall pressures are presented. The predicted locations of the maxima of WSS and the wall pressure can be then correlated with that of the thoracic aorta dissection, and thereby may lead to a useful biological significance. The numerical results also suggest that the effects of low WSS and high OSI tend to cause wall thickening occurred along the inferior wall of the aortic arch and the

Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure.

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Lahiri, Shouri; Schlick, Konrad H; Padrick, Matthew M; Rinsky, Brenda; Gonzalez, Nestor; Jones, Heather; Mayer, Stephan A; Lyden, Patrick D

2018-01-01

Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure. We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure. There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P right and left hemispheric CPI from patients with both elevated and normal right atrial pressure. Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. Copyright © 2017 by the American Society of Neuroimaging.

The dual trigger study: Rationale and study design of a prospective double-blind randomized clinical trial comparing pregnancy rates after co-administration of low dose hCG at the time of GnRH agonist trigger or 35 h later for the prevention of OHSS

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Daniel Griffin

2017-12-01

Full Text Available Ovarian hyperstimulation syndrome (OHSS is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group. The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF after Pituitary Suppression with GnRH Antagonists in Normally Responding Women

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Monzó Ana

2011-01-01

Full Text Available Objective To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. Materials/methods A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH + hp-hMG (n = 51, Group I, hp-hMG (n = 61, Group II, fixed-dose r-FSH (n = 118, Group III, and r-FSH with potential dose adjustment (n = 75, Group IV to subsequently undergo IVF-ICSI. Results During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P < 0.05], but was the group in which more oocytes were recovered [Group I: 9.43 ± 4.99 vs. Group II: 8.96 ± 4.82 vs. Group III: 8.78 ± 3.72 vs. Group IV: 11.62 ± 5.80; P < 0.05]. No significant differences were seen between the groups in terms of clinical and ongoing pregnancy, but among patients in whom two embryos with similar quality parameters (ASEBIR were transferred, the group treated with hp-hMG alone achieved a significantly greater clinical pregnancy rate as compared to all other groups [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05]. Conclusions Although randomized clinical trials should be conducted to achieve a more reliable conclusion, these observations support the concept that stimulation with hp-hMG could be beneficial in normal responders women undergoing pituitary suppression with GnRH antagonists.

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

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Oliveira João

2010-09-01

Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome.

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Seyam, Emaduldin; Hefzy, Enas

2018-07-01

The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle. It is a prospective controlled study, where 250 CCR-PCOD women (n = 250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n = 120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg) was added when a leading follicle reaches 14-16 mm combined with oral Cb in a dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25 IU/L, ± 14 d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3 months for the possible development of any signs and symptoms of OHSS. None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n = 3, 15%) in group B compared with group A (p < .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed. LOD could be considered

Basic study of intrinsic elastography: Relationship between tissue stiffness and propagation velocity of deformation induced by pulsatile flow

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Nagaoka, Ryo; Iwasaki, Ryosuke; Arakawa, Mototaka; Kobayashi, Kazuto; Yoshizawa, Shin; Umemura, Shin-ichiro; Saijo, Yoshifumi

2015-07-01

We proposed an estimation method for a tissue stiffness from deformations induced by arterial pulsation, and named this proposed method intrinsic elastography (IE). In IE, assuming that the velocity of the deformation propagation in tissues is closely related to the stiffness, the propagation velocity (PV) was estimated by spatial compound ultrasound imaging with a high temporal resolution of 1 ms. However, the relationship between tissue stiffness and PV has not been revealed yet. In this study, the PV of the deformation induced by the pulsatile pump was measured by IE in three different poly(vinyl alcohol) (PVA) phantoms of different stiffnesses. The measured PV was compared with the shear wave velocity (SWV) measured by shear wave imaging (SWI). The measured PV has trends similar to the measured SWV. These results obtained by IE in a healthy male show the possibility that the mechanical properties of living tissues could be evaluated by IE.

Increased pulsatility index supports diagnosis of vascular parkinsonism versus idiopathic Parkinson's disease.

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Caba, L M; Ferrairó, J I T; Torres, I M; Costa, J F V; Muñoz, R B; Martin, A L

2017-12-29

The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.

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Maraj, Bharat; Harding-Theobald, Emily; Karaki, Fatima

2018-04-26

Ehlers-Danlos syndrome refers to a spectrum of connective tissue disorders typically caused by mutations in genes responsible for the synthesis of collagen. Patients with Ehlers-Danlos syndrome often exhibit hyperflexibility of joints, increased skin elasticity, and tissue fragility. Vascular Ehlers-Danlos (vEDS) is a subtype of Ehlers-Danlos syndrome with a predilection to involve blood vessels. As such, it often manifests as vascular aneurysms and vessel rupture leading to hemorrhage. There are few reports describing primary prevention of aneurysms in the setting of undiagnosed, suspected vEDS. We present a case of a 30-year-old woman who presents with a pulsatile neck mass found to have multiple arterial aneurysms on imaging, hyperflexibility, and characteristic facial features consistent with vEDS. As described in this case, management of a suspected connective tissue disorder is a multidisciplinary approach including vascular surgery, medical therapy, and genetic testing to confirm the diagnosis. We review literature regarding the care of patients with vascular Ehlers-Danlos as it might pertain to hospitalized patients.

Dynamic time warping and machine learning for signal quality assessment of pulsatile signals

International Nuclear Information System (INIS)

Li, Q; Clifford, G D

2012-01-01

In this work, we describe a beat-by-beat method for assessing the clinical utility of pulsatile waveforms, primarily recorded from cardiovascular blood volume or pressure changes, concentrating on the photoplethysmogram (PPG). Physiological blood flow is nonstationary, with pulses changing in height, width and morphology due to changes in heart rate, cardiac output, sensor type and hardware or software pre-processing requirements. Moreover, considerable inter-individual and sensor-location variability exists. Simple template matching methods are therefore inappropriate, and a patient-specific adaptive initialization is therefore required. We introduce dynamic time warping to stretch each beat to match a running template and combine it with several other features related to signal quality, including correlation and the percentage of the beat that appeared to be clipped. The features were then presented to a multi-layer perceptron neural network to learn the relationships between the parameters in the presence of good- and bad-quality pulses. An expert-labeled database of 1055 segments of PPG, each 6 s long, recorded from 104 separate critical care admissions during both normal and verified arrhythmic events, was used to train and test our algorithms. An accuracy of 97.5% on the training set and 95.2% on test set was found. The algorithm could be deployed as a stand-alone signal quality assessment algorithm for vetting the clinical utility of PPG traces or any similar quasi-periodic signal. (paper)

Dynamic time warping and machine learning for signal quality assessment of pulsatile signals.

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Li, Q; Clifford, G D

2012-09-01

In this work, we describe a beat-by-beat method for assessing the clinical utility of pulsatile waveforms, primarily recorded from cardiovascular blood volume or pressure changes, concentrating on the photoplethysmogram (PPG). Physiological blood flow is nonstationary, with pulses changing in height, width and morphology due to changes in heart rate, cardiac output, sensor type and hardware or software pre-processing requirements. Moreover, considerable inter-individual and sensor-location variability exists. Simple template matching methods are therefore inappropriate, and a patient-specific adaptive initialization is therefore required. We introduce dynamic time warping to stretch each beat to match a running template and combine it with several other features related to signal quality, including correlation and the percentage of the beat that appeared to be clipped. The features were then presented to a multi-layer perceptron neural network to learn the relationships between the parameters in the presence of good- and bad-quality pulses. An expert-labeled database of 1055 segments of PPG, each 6 s long, recorded from 104 separate critical care admissions during both normal and verified arrhythmic events, was used to train and test our algorithms. An accuracy of 97.5% on the training set and 95.2% on test set was found. The algorithm could be deployed as a stand-alone signal quality assessment algorithm for vetting the clinical utility of PPG traces or any similar quasi-periodic signal.

Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

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Mohsen Mehrabi

2012-01-01

Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

Zumbido pulsátil: tratamento com clonazepan e propranolol Pulsatile tinnitus: treatment with clonazepam and propranolol

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Sergio Albertino

2005-02-01

Full Text Available O zumbido pulsátil sincrônico com os batimentos cardíacos é pouco freqüente, sendo de etiologia tanto vascular arterial (malformações, fístulas artério-venosas ou venosa (anormalidades do bulbo jugular, tumor glômico jugular ou timpânico. A identificação precoce da etiologia é essencial para que a terapêutica adequada possa ser instituída. A angioressonância possibilita a identificação de alterações vasculares com maior precisão. Relatamos um caso onde, após o diagnóstico de uma alteração vascular arterial, foi instituído o tratamento com propranolol e clonazepam, com melhora da sintomatologia.Pulsatile tinnitus synchronous with heartbeat is rare and normally has vascular origin: arterial (malformation, arterial anatomical variation or venous (aberrant jugular bulb, glomus tumors, tympanic glomus tumor. Early etiology identification is essential for appropriate treatment to be established. Magnetic angioresonance makes the vascular identification possible and precise. We report a case of arterial anatomical variation in which the treatment was propranolol and clonazepam, showing tinnitus improvement.

Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

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Lv Han

2014-01-01

Full Text Available Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI technique. The present study used unilateral PT patients (n=42 and age-, sex-, and education-matched normal control subjects (n=42 to investigate the changes in structural and amplitude of low-frequency (ALFF of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.

Sustainability.

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Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

2016-10-01

This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.

Efeito da aplicação de hCG ou GnRH sobre a concentração sérica de progesterona e eficiência reprodutiva em porcas Effect of injection of hCG or GnRH on progesterone serum concentration and reproductive efficiency of sows

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L.F.R. Carvalho

2003-12-01

Full Text Available Avaliou-se o efeito da aplicação de diferentes hormônios no quinto dia após a primeira inseminação sobre a concentração sérica de progesterona e sobre as características reprodutivas, em 103 porcas entre o terceirro e sexto parto. As matrizes foram divididas em: grupo-controle (n=35, não tratado, grupo GnRH (n=34, animais submetidos à aplicação intramuscular (IM de 50mcg de um análogo-GnRH no quinto dia após a primeira inseminação, e grupo hCG (n=34, animais submetidos à aplicação IM de 500UI de hCG no quinto dia após a primeira inseminação. A aplicação dos hormônios não influenciou as características reprodutivas taxa de parto, número total de nascidos, número de nascidos vivos e peso da leitegada (P>0,05. Cinco animais de cada grupo foram submetidos a coletas de sangue da veia cava nos dias 3, 5, 8, 12, 21 e 28 após a primeira inseminação para avaliação da concentração sérica de progesterona (ng/ml, utilizando a técnica de radioimunoensaio. Não houve diferença significativa quanto à concentração sérica de progesterona entre os grupos.Two different hormones were administered on the fifth day after the first insemination to evaluate their influence on serum progesterone concentrations and on reproductive efficiency, in multiparous sows between the third and the sixth parturition. The reproductive performance was evaluated in 103 sows distributed into three groups: 1-Control (n=35; 2-GnRH, 50m g of GnRH-analogue, administered IM on the fifth day after the first insemination (n=34; and 3-hCG, 500 IU of hCG administered IM in the fifth day after the first insemination (n=34. No effect (P>0.05 of hormone treatments on farrowing rate, litter size, live born and litter weight was observed. Five sows of each group were blood sampled on days 3, 5, 8, 12, 21, 28, after the first insemination, to evaluate serum progesterone concentrations (ng/ml. Serum progesterone concentrations were not affected (P>0.05 by

Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

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Evans, W S; Anderson, S M; Hull, L T; Azimi, P P; Bowers, C Y; Veldhuis, J D

2001-02-01

How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs. placebo to modulate basal, pulsatile, entropic, and 24-h rhythmic GH secretion driven by a continuous iv infusion of recombinant human GHRH-(1--44)-amide vs. saline in nine healthy postmenopausal women. Volunteers underwent concurrent blood sampling every 10 min for 24 h on four occasions in a prospectively randomized, single blind, within-subject cross-over design (placebo/saline, placebo/GHRH, estradiol/saline, estradiol/GHRH). Intensively sampled serum GH concentrations were quantitated by ultrasensitive chemiluminescence assay. Basal, pulsatile, entropic (feedback-sensitive), and 24-h rhythmic modes of GH secretion were appraised by deconvolution analysis, the approximate entropy (ApEn) statistic, and cosine regression, respectively. ANOVA revealed that continuous iv infusion of GHRH in the estrogen-withdrawn (control) milieu 1) amplified individual basal (P = 0.00011) and pulsatile (P < 10(-13)) GH secretion rates by 12- and 11-fold, respectively; 2) augmented GH secretory burst mass and amplitude each by 10-fold (P < 10(-11)), without altering GH secretory burst frequency, duration, or half-life; 3) increased the disorderliness (ApEn) of GH release patterns (P = 0.0000002); 4) elevated the mesor (cosine mean) and amplitude of the 24-h rhythm in serum GH concentrations by nearly 30-fold (both P < 10(-12)); 5) induced a phase advance in the clocktime of the GH zenith (P = 0.021); and 6) evoked a new 24-h rhythm in GH secretory burst mass with a maximum at 0018 h GH (P < 10(-3)), while damping the mesor of the 24-h rhythm in GH interpulse intervals (P < 0.025). Estradiol supplementation alone 1) increased the 24-h mean and integrated serum GH concentration

Factors affecting synchronization and conception rate after the Ovsynch protocol in lactating Holstein cows.

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Galvão, K N; Santos, J E P

2010-06-01

Objectives were to evaluate risk factors affecting ovulatory responses and conception rate to the Ovsynch protocol. Holstein cows, 466, were submitted to the Ovsynch protocol [day 0, GnRH-1; day 7, prostaglandin (PG) F(2alpha); day 9, GnRH-2] and 103 cows were inseminated 12 h after GnRH-2. Information on parity, days in milk at GnRH-1, body condition, milk yield, exposure to heat stress, pre-synchronization with PGF(2alpha) and the use of progesterone insert from GnRH-1 to PGF(2alpha) was collected. Ovaries were scanned to determine responses to treatments. Overall, 54.7%, 10.6%, 2.2%, 81.1%, 9.0%, 91.5% and 36.9% of the cows ovulated to GnRH-1, multiple ovulated to GnRH-1, ovulated before GnRH-2, ovulated to GnRH-2, multiple ovulated to GnRH-2, experienced corpus luteum (CL) regression and conceived, respectively. Ovulation to GnRH-1 was greater in cows without a CL at GnRH-1, cows with follicles >19 mm and cows not pre-synchronized with PGF(2alpha) 14 days before GnRH-1. Multiple ovulations to GnRH-1 increased in cows without CL at GnRH-1 and cows with follicles Conception rate at 42 days after AI increased in cows with body condition score > 2.75 and cows that ovulated to GnRH-2. Strategies that optimize ovulation to GnRH-2, such as increased ovulation to GnRH-1, should improve response to the Ovsynch protocol.

Mathematical Modeling of Rotary Blood Pumps in a Pulsatile In Vitro Flow Environment.

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Pirbodaghi, Tohid

2017-08-01

Nowadays, sacrificing animals to develop medical devices and receive regulatory approval has become more common, which increases ethical concerns. Although in vivo tests are necessary for development and evaluation of new devices, nonetheless, with appropriate in vitro setups and mathematical models, a part of the validation process can be performed using these models to reduce the number of sacrificed animals. The main aim of this study is to present a mathematical model simulating the hydrodynamic function of a rotary blood pump (RBP) in a pulsatile in vitro flow environment. This model relates the pressure head of the RBP to the flow rate, rotational speed, and time derivatives of flow rate and rotational speed. To identify the model parameters, an in vitro setup was constructed consisting of a piston pump, a compliance chamber, a throttle, a buffer reservoir, and the CentriMag RBP. A 40% glycerin-water mixture as a blood analog fluid and deionized water were used in the hydraulic circuit to investigate the effect of viscosity and density of the working fluid on the model parameters. First, model variables were physically measured and digitally acquired. Second, an identification algorithm based on regression analysis was used to derive the model parameters. Third, the completed model was validated with a totally different set of in vitro data. The model is usable for both mathematical simulations of the interaction between the pump and heart and indirect pressure measurement in a clinical context. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Sigmoid sinus diverticulum and pulsatile tinnitus - Analysis of CT scans from 15 cases

International Nuclear Information System (INIS)

Liu, Zhaohui; Wang, Zhenchang; Xian, Junfang; Wang, Yongzhe; Liang, Xihong; Chen, Chengfang; Gong, Shusheng; Ma, Xiaobo; Li, Yi

2013-01-01

Background: Although the imaging features of sigmoid sinus diverticulum induced pulsatile tinnitus (PT) have been presented in some extent, detailed imaging findings still have not been systematically evaluated and precise diagnostic radiographic criteria has not been established. Purpose: To examine the computed tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with PT. Material and Methods: Fifteen PT patients with sigmoid sinus diverticula proven by surgery were recruited after consenting. CT images of 15 patients were obtained and analyzed, including features of diverticula, brain venous systems, integrity of the sigmoid plate, and the degree of temporal bone pneumatization. Results: Sigmoid sinus diverticulum was located on the same side of PT in 15 patients. Diverticula originated at the superior curve of the sigmoid sinus in 11 patients and the descending segment of the sigmoid sinus in four patients. Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in 12 patients and mastoid cortex in three patients. Among eight patients with unilateral dominant brain venous systems, the diverticula were seen on the dominant side in seven patients and non-dominant side in one patient. In contrast, the other seven patients showed co-dominant brain venous systems, with three presenting diverticula on the right side and four on the left. More notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients. In addition, temporal bone hyper-pneumatization was found in nine patients, good and moderate pneumatization in three patients, respectively. Conclusion: Dehiscent sigmoid plate and extensive temporal bone pneumatization are two important imaging characteristics of the PT induced by sigmoid sinus diverticulum

Sigmoid sinus diverticulum and pulsatile tinnitus - Analysis of CT scans from 15 cases

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Liu, Zhaohui; Wang, Zhenchang; Xian, Junfang; Wang, Yongzhe; Liang, Xihong [Dept. of Radiology, Capital Medical Univ., Beijing Tongren Hospital, Beijing (China); Chen, Chengfang; Gong, Shusheng; Ma, Xiaobo; Li, Yi [Dept. of Otolaryngology Head and Neck Surgery, Capital Medical Univ., Beijing Tongren Hospital, Beijing (China)

2013-09-15

Background: Although the imaging features of sigmoid sinus diverticulum induced pulsatile tinnitus (PT) have been presented in some extent, detailed imaging findings still have not been systematically evaluated and precise diagnostic radiographic criteria has not been established. Purpose: To examine the computed tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with PT. Material and Methods: Fifteen PT patients with sigmoid sinus diverticula proven by surgery were recruited after consenting. CT images of 15 patients were obtained and analyzed, including features of diverticula, brain venous systems, integrity of the sigmoid plate, and the degree of temporal bone pneumatization. Results: Sigmoid sinus diverticulum was located on the same side of PT in 15 patients. Diverticula originated at the superior curve of the sigmoid sinus in 11 patients and the descending segment of the sigmoid sinus in four patients. Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in 12 patients and mastoid cortex in three patients. Among eight patients with unilateral dominant brain venous systems, the diverticula were seen on the dominant side in seven patients and non-dominant side in one patient. In contrast, the other seven patients showed co-dominant brain venous systems, with three presenting diverticula on the right side and four on the left. More notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients. In addition, temporal bone hyper-pneumatization was found in nine patients, good and moderate pneumatization in three patients, respectively. Conclusion: Dehiscent sigmoid plate and extensive temporal bone pneumatization are two important imaging characteristics of the PT induced by sigmoid sinus diverticulum.

An original valveless artificial heart providing pulsatile flow tested in mock circulatory loops.

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Tozzi, Piergiorgio; Maertens, Audrey; Emery, Jonathan; Joseph, Samuel; Kirsch, Matthias; Avellan, François

2017-11-24

We present the test bench results of a valveless total artificial heart that is potentially compatible with the pediatric population. The RollingHeart is a valveless volumetric pump generating pulsatile flow. It consists of a single spherical cavity divided into 4 chambers by 2 rotating disks. The combined rotations of both disks produce changes in the volumes of the 4 cavities (suction and ejection). The blood enters/exits the spherical cavity through 4 openings that are symmetrical to the fixed rotation axis of the first disk.Mock circulatory system: The device pumps a 37% glycerin solution through 2 parallel circuits, simulating the pulmonary and systemic circulations. Flow rates are acquired with a magnetic inductive flowmeter, while pressure sensors collect pressure in the left and right outflow and inflow tracts.In vitro test protocol: The pump is run at speeds ranging from 20 to 180 ejections per minute. The waveform of the pressure generated at the inflow and outflow of the 4 chambers and the flow rate in the systemic circulation are measured. At an ejection rate of 178 min-1, the RollingHeart pumps 5.3 L/min for a systemic maximal pressure gradient of 174 mmHg and a pulmonary maximal pressure gradient of 75 mmHg. The power input was 14 W, corresponding to an efficiency of 21%. The RollingHeart represents a new approach in the domain of total artificial heart. This preliminary study endorses the feasibility of a single valveless device acting as a total artificial heart.

Sustainable diets within sustainable food systems.

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Meybeck, Alexandre; Gitz, Vincent

2017-02-01

Sustainable diets and sustainable food systems are increasingly explored by diverse scientific disciplines. They are also recognised by the international community and called upon to orient action towards the eradication of hunger and malnutrition and the fulfilment of sustainable development goals. The aim of the present paper is to briefly consider some of the links between these two notions in order to facilitate the operationalisation of the concept of sustainable diet. The concept of sustainable diet was defined in 2010 combining two totally different perspectives: a nutrition perspective, focused on individuals, and a global sustainability perspective, in all its dimensions: environmental, economic and social. The nutrition perspective can be easily related to health outcomes. The global sustainability perspective is more difficult to analyse directly. We propose that it be measured as the contribution of a diet to the sustainability of food systems. Such an approach, covering the three dimensions of sustainability, enables identification of interactions and interrelations between food systems and diets. It provides opportunities to find levers of change towards sustainability. Diets are both the results and the drivers of food systems. The drivers of change for those variously involved, consumers and private individuals, are different, and can be triggered by different dimensions (heath, environment, social and cultural). Combining different dimensions and reasons for change can help facilitate the transition to sustainable diets, recognising the food system's specificities. The adoption of sustainable diets can be facilitated and enabled by food systems, and by appropriate policies and incentives.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

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Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

2011-10-01

Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Flow visualization of three-dimensionality inside the 12 cc Penn State pulsatile pediatric ventricular assist device.

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Roszelle, Breigh N; Deutsch, Steven; Manning, Keefe B

2010-02-01

In order to aid the ongoing concern of limited organ availability for pediatric heart transplants, Penn State has continued development of a pulsatile Pediatric Ventricular Assist Device (PVAD). Initial studies of the PVAD observed an increase in thrombus formation due to differences in flow field physics when compared to adult sized devices, which included a higher degree of three-dimensionality. This unique flow field brings into question the use of 2D planar particle image velocimetry (PIV) as a flow visualization technique, however the small size and high curvature of the PVAD make other tools such as stereoscopic PIV impractical. In order to test the reliability of the 2D results, we perform a pseudo-3D PIV study using planes both parallel and normal to the diaphragm employing a mock circulatory loop containing a viscoelastic fluid that mimics 40% hematocrit blood. We find that while the third component of velocity is extremely helpful to a physical understanding of the flow, particularly of the diastolic jet and the development of a desired rotational pattern, the flow data taken parallel to the diaphragm is sufficient to describe the wall shear rates, a critical aspect to the study of thrombosis and design of such pumps.

Pulsatility Index as a Diagnostic Parameter of Reciprocating Wall Shear Stress Parameters in Physiological Pulsating Waveforms.

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Idit Avrahami

Full Text Available Arterial wall shear stress (WSS parameters are widely used for prediction of the initiation and development of atherosclerosis and arterial pathologies. Traditional clinical evaluation of arterial condition relies on correlations of WSS parameters with average flow rate (Q and heart rate (HR measurements. We show that for pulsating flow waveforms in a straight tube with flow reversals that lead to significant reciprocating WSS, the measurements of HR and Q are not sufficient for prediction of WSS parameters. Therefore, we suggest adding a third quantity-known as the pulsatility index (PI-which is defined as the peak-to-peak flow rate amplitude normalized by Q. We examine several pulsating flow waveforms with and without flow reversals using a simulation of a Womersley model in a straight rigid tube and validate the simulations through experimental study using particle image velocimetry (PIV. The results indicate that clinically relevant WSS parameters such as the percentage of negative WSS (P[%], oscillating shear index (OSI and the ratio of minimum to maximum shear stress rates (min/max, are better predicted when the PI is used in conjunction with HR and Q. Therefore, we propose to use PI as an additional and essential diagnostic quantity for improved predictability of the reciprocating WSS.

Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.

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Taha, Ehab I

2016-09-01

Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC 0-∞ , C max , T max , t 1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.

The Two Populations of Kisspeptin Neurons Are Involved in the Ram-Induced LH Pulsatile Secretion and LH Surge in Anestrous Ewes.

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Fabre-Nys, Claude; Cognié, Juliette; Dufourny, Laurence; Ghenim, Meriem; Martinet, Stephanie; Lasserre, Olivier; Lomet, Didier; Millar, Robert P; Ohkura, Satoshi; Suetomi, Yuta

2017-11-01

Exposure to a ram during spring stimulates luteinizing hormone (LH) secretion and can induce ovulation in sexually quiescent ewes ("ram effect"). Kisspeptin (Kiss) present in the arcuate nucleus (ARC) and the preoptic area (POA) is a potent stimulators of LH secretion. Our aim was to investigate whether Kiss neurons mediate the increase in LH secretion during the ram effect. With double immunofluorescent detection, we identified Kiss neurons (Kiss IR) activated (Fos IR) by exposure to a ram for 2 hours (M2) or 12 hours (M12) or to ewes for 2 hours (C). The density of cells Kiss + Fos IR and the proportion of Kiss IR cells that were also Fos IR cells were higher in M2 and M12 than in C in ARC (P populations of Kiss neurons are involved in the ram-induced pulsatile LH secretion and in the LH surge. Copyright © 2017 Endocrine Society.

Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

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Wijethilake, Chaminda

2017-07-01

This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing sustainable remediation frameworks using sustainability principles.

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Ridsdale, D Reanne; Noble, Bram F

2016-12-15

The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders

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Shamim Pilehvari

2016-05-01

Full Text Available Objective: To compare the pregnancy outcomes achieved by in vitro fertilization (IVF between minimal stimulation and conventional antagonist protocols in poor ovarian responders (PORs.Materials and methods: In this randomized controlled trial, 77 PORs undergoing IVF were selected and divided into two groups. First group was the minimal stimulation group (n = 42 receiving 100 mg/day clomiphene citrate on day 2of the cycle for 5 day that was followed by150IU/day human menopausal gonadotropin (hMG on day 5 of the cycle. Second group was the conventional group (n = 35 receiving at least 300 IU/daygonadotropin on day 2 of the cycle. Gonadotropin-releasing hormone (GnRH antagonist protocol was applied for both groups according to flexible protocol. Number of retrieved oocytes and chemical pregnancy rate were the main outcomes.Results: There was no difference in number ofretrieved oocyte and pregnancy rate (2.79 ± 1.96 vs. 2.20 ± 1.71 and 5.6% vs. 4.1%; p > 0.05 between both groups. The gonadotropin dose used in the minimal stimulation group was lower than conventional group (1046 ± 596 vs. 2806 ± 583.Conclusion: Minimal stimulation protocol with lower gonadotropin used is likely to be considered as a patient- friendly and cost-effective substitute for PORs. 

Impaired Central Pulsatile Hemodynamics in Children and Adolescents With Marfan Syndrome.

Science.gov (United States)

Grillo, Andrea; Salvi, Paolo; Marelli, Susan; Gao, Lan; Salvi, Lucia; Faini, Andrea; Trifirò, Giuliana; Carretta, Renzo; Pini, Alessandro; Parati, Gianfranco

2017-11-07

Marfan syndrome is characterized by aortic root dilation, beginning in childhood. Data about aortic pulsatile hemodynamics and stiffness in pediatric age are currently lacking. In 51 young patients with Marfan syndrome (12.0±3.3 years), carotid tonometry was performed for the measurement of central pulse pressure, pulse pressure amplification, and aortic stiffness (carotid-femoral pulse wave velocity). Patients underwent an echocardiogram at baseline and at 1 year follow-up and a genetic evaluation. Pathogenetic fibrillin-1 mutations were classified between "dominant negative" and "haploinsufficient." The hemodynamic parameters of patients were compared with those of 80 sex, age, blood pressure, and heart-rate matched controls. Central pulse pressure was significantly higher (38.3±12.3 versus 33.6±7.8 mm Hg; P =0.009), and pulse pressure amplification was significantly reduced in Marfan than controls (17.9±15.3% versus 32.3±17.4%; P Marfan and controls (4.98±1.00 versus 4.75±0.67 m/s). In the Marfan group, central pulse pressure and pulse pressure amplification were independently associated with aortic diameter at the sinuses of Valsalva (respectively, β=0.371, P =0.010; β=-0.271, P =0.026). No significant difference in hemodynamic parameters was found according to fibrillin-1 genotype. Patients who increased aortic Z-scores at 1-year follow-up presented a higher central pulse pressure than the remaining (42.7±14.2 versus 32.3±5.9 mm Hg; P =0.004). Central pulse pressure and pulse pressure amplification were impaired in pediatric Marfan syndrome, and associated with aortic root diameters, whereas aortic pulse wave velocity was similar to that of a general pediatric population. An increased central pulse pressure was present among patients whose aortic dilatation worsened at 1-year follow-up. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Pharmacokinetics and Bioavailability of the GnRH Analogs in the Form of Solution and Zn2+-Suspension After Single Subcutaneous Injection in Female Rats.

Science.gov (United States)

Suszka-Świtek, Aleksandra; Ryszka, Florian; Dolińska, Barbara; Dec, Renata; Danch, Alojzy; Filipczyk, Łukasz; Wiaderkiewicz, Ryszard

2017-04-01

Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem. Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn 2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method. The Extent of Biological Availability (EBA), calculated on the base of AUC 0-∞ , showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted

Corporate Sustainability Reporting in the BIST Sustainability Index

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Burcu Demirel

2016-11-01

Full Text Available In recent years, there is a growing focus on corporate operations especially since the publication of the first environmental reports in 1989. Companies have started to publish information about its environmental, social and sustainability policies. The study examines the sustainability reporting elements of Borsa Istanbul Sustainability Index (BIST in Turkey and to evaluate which elements is most vital in this context. This study will begin with the sustainability reporting that will be examined under the roof of corporation sustainability and end with the examination of sustainability reports of 15 firms, which are included in the BIST Sustainability Index in Turkey, and a content analysis. The reports of companies under study were taken from special web site and GRI (Global Reporting Initiative database of companies. Being the first study in examining the sustainability report of companies in BIST Sustainability Index, it is expected to contribute in literature about sustainability reporting recently started to gain importance in Turkey. Overall our findings suggest that the sustainability index established in Turkey is still in development stage, but the enterprises in the endeavor are working day by day to develop the sustainability qualities.

Spatial-temporal three-dimensional ultrasound plane-by-plane active cavitation mapping for high-intensity focused ultrasound in free field and pulsatile flow.

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Ding, Ting; Hu, Hong; Bai, Chen; Guo, Shifang; Yang, Miao; Wang, Supin; Wan, Mingxi

2016-07-01

Cavitation plays important roles in almost all high-intensity focused ultrasound (HIFU) applications. However, current two-dimensional (2D) cavitation mapping could only provide cavitation activity in one plane. This study proposed a three-dimensional (3D) ultrasound plane-by-plane active cavitation mapping (3D-UPACM) for HIFU in free field and pulsatile flow. The acquisition of channel-domain raw radio-frequency (RF) data in 3D space was performed by sequential plane-by-plane 2D ultrafast active cavitation mapping. Between two adjacent unit locations, there was a waiting time to make cavitation nuclei distribution of the liquid back to the original state. The 3D cavitation map equivalent to the one detected at one time and over the entire volume could be reconstructed by Marching Cube algorithm. Minimum variance (MV) adaptive beamforming was combined with coherence factor (CF) weighting (MVCF) or compressive sensing (CS) method (MVCS) to process the raw RF data for improved beamforming or more rapid data processing. The feasibility of 3D-UPACM was demonstrated in tap-water and a phantom vessel with pulsatile flow. The time interval between temporal evolutions of cavitation bubble cloud could be several microseconds. MVCF beamformer had a signal-to-noise ratio (SNR) at 14.17dB higher, lateral and axial resolution at 2.88times and 1.88times, respectively, which were compared with those of B-mode active cavitation mapping. MVCS beamformer had only 14.94% time penalty of that of MVCF beamformer. This 3D-UPACM technique employs the linear array of a current ultrasound diagnosis system rather than a 2D array transducer to decrease the cost of the instrument. Moreover, although the application is limited by the requirement for a gassy fluid medium or a constant supply of new cavitation nuclei that allows replenishment of nuclei between HIFU exposures, this technique may exhibit a useful tool in 3D cavitation mapping for HIFU with high speed, precision and resolution

Pulsatility Index of Blood Echogenicity of the Human Radial and Common Carotid Arteries: Relation with Age and Stroke

International Nuclear Information System (INIS)

Bok, Tae Hoon; Kong, Qi; Nam, Kweon Ho; Choi, Jay Chol; Paeng, Dong Guk

2012-01-01

In the present paper, the ultrasound blood images were measured at both the human radial artery(RA) and common carotid artery(CCA), depending on the age, and the pulsatility index of blood echogenicity(PIBE) was analyzed. In addition, the ultrasound blood images were measured at both RA and CCA of both the stroke patients and the control group, and PIBE was compared. PIBE of RA for the young group was similar with that for the old group (0.13±0.21 and 0.16±0.03). PIBE of CCA for the young group, however, was larger than that for the old group (0.70±0.21 and 0.32±0.01), and was more variable depending on the subject. Similarly, the fibrinogen concentrations of the patients (336±61 and 340±126 mg/dl) were more than that of the control group (264±38 and 43 mg/dl), for both RA and CCA. The results indicate the possibility of the ultrasonic test on the correlation between erythrocyte aggregation and stroke, and it is expected that the in-vivo EA measurement would be clinically useful.

Pulsatility index variations using two different transit-time flowmeters in coronary artery bypass surgery.

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Nordgaard, Håvard B; Vitale, Nicola; Astudillo, Rafael; Renzulli, Attilio; Romundstad, Pål; Haaverstad, Rune

2010-05-01

Transit-time flow measurement is widely accepted as an intra-operative assessment in coronary artery bypass grafting (CABG). However, the two most commonly applied flowmeters, manufactured by MediStim ASA and Transonic Inc., have different default filter settings of 20 and 10 Hz, respectively. This may cause different flow measurements, which will influence the reported results. The aim was to compare pulsatility index (PI) values recorded by the MediStim and Transonic flowmeters in two different clinical settings: (1) analysis of the flow patterns recorded simultaneously by both flowmeters in the same CABGs; and (2) evaluation of flow patterns under different levels of filter settings in the same grafts. Graft flow and PI were measured using the two different flowmeters simultaneously in 19 bypass grafts. Finally, eight grafts were assessed under different digital filter settings at 5, 10, 20, 30, 50 and 100 Hz. The Transonic flowmeter provided substantially lower PI as compared with the MediStim flowmeter. By increasing the filter setting in the flowmeter, PI increased considerably. The Transonic flowmeter displayed a lower PI than the MediStim, due to a lower filter setting. In the Transonic,flow signals are filtered at a lower level, rendering a 'smoother' pattern of flow curves. Because different filter settings determine different PIs, caution must be taken when flow values and flowmeters are compared. The type of flowmeter should be indicated whenever graft flow measurements and derived indexes are provided [corrected]. Copyright 2009 European Association for Cardio-Thoracic Surgery. All rights reserved.

Interdependences between sustainable development and sustainable economy

OpenAIRE

Emilia Mioara CÂMPEANU; Carmen Valentina RĂDULESCU

2014-01-01

Sustainable development and sustainable economy are mostly used concepts. Understanding clearly their meaning allows their use in an appropriate context and, therefore, their boundaries in terms of theoretical and practical approaches on which occasion it can be given their interdependencies. The paper aim is to analyze the interdependences between sustainable development and sustainable economy.

Carotid flow pulsatility is higher in women with greater decrement in gait speed during multi-tasking.

Science.gov (United States)

Gonzales, Joaquin U; James, C Roger; Yang, Hyung Suk; Jensen, Daniel; Atkins, Lee; Al-Khalil, Kareem; O'Boyle, Michael

2017-05-01

Central arterial hemodynamics is associated with cognitive impairment. Reductions in gait speed during walking while performing concurrent tasks known as dual-tasking (DT) or multi-tasking (MT) is thought to reflect the cognitive cost that exceeds neural capacity to share resources. We hypothesized that central vascular function would associate with decrements in gait speed during DT or MT. Gait speed was measured using a motion capture system in 56 women (30-80y) without mild-cognitive impairment. Dual-tasking was considered walking at a fast-pace while balancing a tray. Multi-tasking was the DT condition plus subtracting by serial 7's. Applanation tonometry was used for measurement of aortic stiffness and central pulse pressure. Doppler-ultrasound was used to measure blood flow velocity and β-stiffness index in the common carotid artery. The percent change in gait speed was larger for MT than DT (14.1±11.2 vs. 8.7±9.6%, p decrement (third tertile) as compared to women with less decrement (first tertile) in gait speed during MT after adjusting for age, gait speed, and task error. Carotid pulse pressure and β-stiffness did not contribute to these tertile differences. Elevated carotid flow pulsatility and resistance are characteristics found in healthy women that show lower cognitive capacity to walk and perform multiple concurrent tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Effects of a Microdose GnRH Agonist Flare Regimen Administered to Poor Responders Undergoing ART Cycles

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Aflatoonian Abbas

2009-10-01

Full Text Available The microdose GnRH agonist (GnRH-a flare protocol may have a particular value for previously poor responders in whom it has been observed to stimulate dramatic increases in serum FSH. The Purpose of this study was to determine the effects of microdose GnRH-a in poor responders. This is a clinical trial with before and after design. This study was done in Research and Clinical Center for Infertility (Shahid Sadoughi University, Yazd, Iran and Madar Hospital, Yazd, Iran. In this study, 61 poor responders volunteered for in vitro fertilization (IVF or intracytoplacmic sperm injection (ICSI. The volunteers were divided into two age groups (group A, 20 - 34; group B, 35 - 40 and received low dose oral contraceptive pills for 21 days, then 40µg of subcutaneous buserelin 2 times/day from day 3 of the cycle and human menopausal gonadotropin (hMG 3 ampoules/day from day 5. Main Outcome measures were number of follicles, oocytes and embryos, and pregnancy rate (PR. These measures were then compared with those of the previous cycle. There were significant differences in all parameters (P < 0.05. Pregnancy occurred in 3 women (5%. There was no significant difference in number of follicles, oocytes and embryo between two age groups (P > 0.05. Use of microdose GnRH-a plus HMG for controlled ovarian hyperstimulation in IVF or ICSI cycles can lead to formation of more follicles, oocyte and embryo in poor responders.

Grassland Sustainability

Science.gov (United States)

Deborah U. Potter; Paulette L. Ford

2004-01-01

In this chapter we discuss grassland sustainability in the Southwest, grassland management for sustainability, national and local criteria and indicators of sustainable grassland ecosystems, and monitoring for sustainability at various scales. Ecological sustainability is defined as: [T]he maintenance or restoration of the composition, structure, and processes of...

Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

Science.gov (United States)

Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

2005-10-01

Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

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Berga, Sarah L; Loucks, Tammy L

2006-12-01

Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

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Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Textiles and clothing sustainability sustainable technologies

CERN Document Server

2017-01-01

This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development.

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Miller, Nichol L G; Wevrick, Rachel; Mellon, Pamela L

2009-01-15

Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.

Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development

Science.gov (United States)

Miller, Nichol L.G.; Wevrick, Rachel; Mellon, Pamela L.

2009-01-01

Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS. PMID:18930956

Changes in the 5-HT2A receptor system in the pre-mammillary hypothalamus of the ewe are related to regulation of LH pulsatile secretion by an endogenous circannual rhythm

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Karsch Fred J

2003-01-01

Full Text Available Abstract Background We wanted to determine if changes in the expression of serotonin 2A receptor (5HT2A receptor gene in the premammillary hypothalamus are associated with changes in reproductive neuroendocrine status. Thus, we compared 2 groups of ovariectomized-estradiol-treated ewes that expressed high vs low LH pulsatility in two different paradigms (2 groups per paradigm: (a refractoriness (low LH secretion or not (high LH secretion to short days in pineal-intact Ile-de-France ewes (RSD and (b endogenous circannual rhythm (ECR in free-running pinealectomized Suffolk ewes in the active or inactive stage of their reproductive rhythm. Results In RSD ewes, density of 5HT2A receptor mRNA (by in situ hybridization was significantly higher in the high LH group (25.3 ± 1.4 vs 21.4 ± 1.5 grains/neuron, P 3H-Ketanserin binding (a specific radioligand of the median part of the premammillary hypothalamus tended to be higher in the high group (29.1 ± 4.0 vs 24.6 ± 4.2 fmol/mg tissu-equivalent; P A receptor mRNA and 3H-Ketanserin binding were both significantly higher in the high LH group (20.8 ± 1.6 vs 17.0 ± 1.5 grains/neuron, P Conclusions We conclude that these higher 5HT2A receptor gene expression and binding activity of 5HT2A receptor in the premammillary hypothalamus are associated with stimulation of LH pulsatility expressed before the development of refractoriness to short days and prior to the decline of reproductive neuroendocrine activity during expression of the endogenous circannual rhythm.

20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

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Chehab, Farid F

2014-10-01

The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. © 2014 Society for Endocrinology.